10 results on '"Lea T. Grinberg"'
Search Results
2. Morphometric measurements of systemic atherosclerosis and visceral fat: Evidence from an autopsy study
- Author
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Renata Eloah de Lucena Ferretti-Rebustini, Fernanda Marinho Campos, Aline Nishizawa, Renata Elaine Paraizo Leite, Wilson Jacob-Filho, Claudia K. Suemoto, Carlos Augusto Pasqualucci, José Marcelo Farfel, Márcio Sommer Bittencourt, Daniela Souza Farias-Itao, Karen Cristina Souza da Silva, Lea T. Grinberg, and Sun, Qinghua
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Male ,Aging ,Cerebral arteries ,lcsh:Medicine ,Adipose tissue ,Autopsy ,030204 cardiovascular system & hematology ,Cardiovascular ,Pathology and Laboratory Medicine ,Vascular Medicine ,Biochemistry ,Fats ,0302 clinical medicine ,80 and over ,Medicine and Health Sciences ,lcsh:Science ,Coronary Arteries ,Aorta ,Stenosis ,Aged, 80 and over ,Aortic atherosclerosis ,Multidisciplinary ,Confounding ,Arteries ,Middle Aged ,Lipids ,Heart Disease ,Carotid Arteries ,medicine.anatomical_structure ,Cardiology ,Female ,Anatomy ,Research Article ,Adult ,medicine.medical_specialty ,General Science & Technology ,Surgical and Invasive Medical Procedures ,and over ,Intra-Abdominal Fat ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,medicine.artery ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Heart Disease - Coronary Heart Disease ,Aged ,business.industry ,lcsh:R ,Biology and Life Sciences ,Cerebral Arteries ,Atherosclerosis ,medicine.disease ,Coronary arteries ,Cardiovascular Anatomy ,Blood Vessels ,lcsh:Q ,business ,030217 neurology & neurosurgery - Abstract
Author(s): Nishizawa, Aline; Suemoto, Claudia K; Farias-Itao, Daniela S; Campos, Fernanda M; Silva, Karen CS; Bittencourt, Marcio S; Grinberg, Lea T; Leite, Renata EP; Ferretti-Rebustini, Renata EL; Farfel, Jose M; Jacob-Filho, Wilson; Pasqualucci, Carlos A | Abstract: BACKGROUND:Morphometric measurements of systemic atherosclerosis and direct quantification of visceral fat are only possible using materials from autopsy studies. However, the few autopsy studies that have investigated the association of visceral fat with atherosclerosis had small sample sizes and focused on coronary arteries of young or middle-aged White subjects. We aimed to investigate the association of pericardial fat (PF) and abdominal visceral fat (AVF) with atherosclerosis in the aorta, coronary, carotid, and cerebral arteries in a large autopsy study. MATERIALS AND METHODS:We evaluated deceased subjects aged 30 years or above. We dissected and weighted the PF and the AVF and evaluated the atherosclerotic burden in the aorta, as well as the carotid, coronary, and cerebral arteries using morphometric measurements. We also investigated the interaction of PF and AVF with age regarding the atherosclerotic burden. RESULTS:The mean age of the 240 included subjects was 64.8±15.3 years, and 63% was male. Greater PF was associated with a higher degree of aortic atherosclerosis after adjusting for confounding variables (coefficient = 4.39, 95% CI = 0.83; 7.94, p = 0.02). Greater AVF was associated with a higher coronary stenosis index (coefficient = 1.49, 95% CI = 0.15; 2.83, p = 0.03) and a greater number of coronary plaques (coefficient = 0.71, 95% CI = 0.24; 1.19, p = 0.003). We did not find an association of PF or AVF with carotid or cerebral atherosclerotic burden. We found a significant interaction of AVF (coefficient = -0.08; 95% CI = -0.14; -0.02, p = 0.009) and PF (coefficient = -0.87, 95% CI = -1.70; -0.04, p = 0.04) with age regarding carotid artery atherosclerotic burden. CONCLUSIONS:Greater AVF was associated with greater atherosclerotic burden and extent in coronary arteries, while greater PF correlated with a higher degree of atherosclerosis in the aorta.
- Published
- 2017
3. Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study
- Author
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Mayana Zatz, Renata Eloah de Lucena Ferretti-Rebustini, Renata Elaine Paraizo Leite, Claudia K. Suemoto, Luciana Soterio, Roberta Diehl Rodriguez, Carlos Augusto Pasqualucci, Ricardo Nitrini, Michel S Naslavsky, Tarcila Marinho Cippiciani, Lea T. Grinberg, José Marcelo Farfel, Alexandre Dias Porto Chiavegatto Filho, Sonia Maria Dozzi Brucki, Raphael Ribeiro Spera, and Wilson Jacob-Filho
- Subjects
Male ,0301 basic medicine ,Pediatrics ,Dementia with Lewy bodies ,lcsh:Medicine ,Pathology and Laboratory Medicine ,Cognition ,0302 clinical medicine ,Medicine and Health Sciences ,Cognitive Impairment ,Aged, 80 and over ,Cognitive Neurology ,Neurodegenerative Diseases ,General Medicine ,ESTUDOS TRANSVERSAIS ,Middle Aged ,3. Good health ,Neurology ,Female ,Alzheimer's disease ,Brazil ,Research Article ,medicine.medical_specialty ,Clinical Dementia Rating ,Cognitive Neuroscience ,Cerebrovascular Diseases ,Vascular Dementia ,03 medical and health sciences ,Signs and Symptoms ,Alzheimer Disease ,Diagnostic Medicine ,Informant Questionnaire on Cognitive Decline in the Elderly ,Mental Health and Psychiatry ,mental disorders ,medicine ,Humans ,Dementia ,Vascular dementia ,Aged ,Hippocampal sclerosis ,Lewy body ,business.industry ,Dementia, Vascular ,lcsh:R ,Biology and Life Sciences ,Alzheimer Disease Diagnosis and Management ,medicine.disease ,Cross-Sectional Studies ,030104 developmental biology ,Lesions ,Cognitive Science ,business ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Background Clinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis. Methods and findings In this cross-sectional study, we describe clinical and neuropathological variables related to cognitive impairment in 1,092 participants (mean age = 74 y, 49% male, 69% white, and mean education = 4 y). Cognitive function was investigated using the Clinical Dementia Rating (CDR) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE); neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory (NPI). Associations between neuropathological lesions and cognitive impairment were investigated using ordinal logistic regression. We developed a neuropathological comorbidity (NPC) score and compared it to CDR, IQCODE, and NPI scores. We also described and compared the frequency of neuropathological diagnosis to clinical diagnosis of dementia subtype. Forty-four percent of the sample met criteria for neuropathological diagnosis. Among these participants, 50% had neuropathological diagnoses of Alzheimer disease (AD), and 35% of vascular dementia (VaD). Neurofibrillary tangles (NFTs), hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and Lewy body disease were independently associated with cognitive impairment. Higher NPC scores were associated with worse scores in the CDR sum of boxes (β = 1.33, 95% CI 1.20–1.46), IQCODE (β = 0.14, 95% CI 0.13–0.16), and NPI (β = 1.74, 95% CI = 1.33–2.16). Compared to neuropathological diagnoses, clinical diagnosis had high sensitivity to AD and high specificity to dementia with Lewy body/Parkinson dementia. The major limitation of our study is the lack of clinical follow-up of participants during life. Conclusions NFT deposition, vascular lesions, and high NPC scorewere associated with cognitive impairment in a unique Brazilian sample with low education. Our results confirm the high prevalence of neuropathological diagnosis in older adults and the mismatch between clinical and neuropathological diagnoses., In a postmortem analysis, Lea Grinberg and colleagues examine neuropathological diagnoses in a sample of older adults from Brazil., Author summary Why was this study done? Fifty-eight percent of people with dementia live in low- and middle-income countries (LMICs), and this percentage is expected to increase to 71% by 2050. Definitive diagnosis of dementia etiology requires a neuropathological exam. In high-income countries (HICs), Alzheimer disease (AD) is the most common cause of dementia, usually coexisting with other neurodegenerative and vascular lesions. Almost no neuropathological information is available for LMICs; therefore, we investigated the frequency of neurodegenerative and cerebrovascular lesions and their correlation with cognitive and neuropsychiatric symptoms in a clinicopathological study with 1,092 admixed older participants from Brazil. What did the researchers do and find? In a cross-sectional study, we described the frequency of the most common causes of dementia, as well as the correspondence between clinical and neuropathological diagnosis, in a large population-based series with 1,092 older adults from a LMIC. We developed a comorbidity neuropathological score to account for the association between the coexistence of cerebral lesions and cognitive and neuropsychiatric symptoms. Forty-four percent of participants had enough neuropathological lesions to fulfill the criteria for at least one neuropathological diagnosis. AD was the most common diagnosis (50%), followed by vascular dementia (35%). Higher neuropathological comorbidity associated with worse cognition and a higher burden of neuropsychiatric symptoms. What do these findings mean? In a large sample from a LMIC, dementia subtypes were similar to those seen in series from HICs. Although vascular dementia was not as frequent as AD, its frequency was relatively higher than in HIC series.
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- 2017
4. Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer's disease
- Author
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Maria Dirlei Begnami, Helena Brentani, Renata E.L. Ferretti, Wilson Jacob-Filho, Carlos Eduardo Pereira, Antonio Campos, Rafael Malagoli Rocha, Isabela Werneck da Cunha, Ana Cecilia Feio dos Santos, Lea T. Grinberg, Aderbal R. T. Silva, Dirce Maria Carraro, and José Marcelo Farfel
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Male ,Pathology ,medicine.medical_specialty ,DNA Repair ,DNA damage ,DNA repair ,Histopathology ,lcsh:Medicine ,Apoptosis ,Neuropathology ,Biology ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Hippocampus ,Alzheimer Disease ,Diagnostic Medicine ,Mental Health and Psychiatry ,mental disorders ,Medicine and Health Sciences ,medicine ,Humans ,Dementia ,Senile plaques ,lcsh:Science ,Aged, 80 and over ,Neurons ,Multidisciplinary ,Cell Cycle ,lcsh:R ,Neurodegenerative Diseases ,DNA ,Cell cycle ,medicine.disease ,Oxidative Stress ,Neurology ,Tissue Array Analysis ,Anatomical Pathology ,Female ,lcsh:Q ,Alzheimer's disease ,Transcriptome ,Oxidative stress ,DNA Damage ,Research Article - Abstract
Alzheimer's disease (AD) is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles). Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p27Kip1, phospho-Rb and E2F1) through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA) composed of three groups: I) "clinical-pathological AD" (CP-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and clinical dementia (CDR ≥ 2, IQCODE>3.8); II) "pathological AD" (P-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and without cognitive impairment (CDR 0, IQCODE
- Published
- 2014
5. Sexual dimorphism in the human olfactory bulb: females have more neurons and glial cells than males
- Author
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Ana V. Oliveira-Pinto, Lea T. Grinberg, Claudia K. Suemoto, Renan Amaral Coutinho, José Marcelo Farfel, Roberto Lent, Ana Tereza Di Lorenzo Alho, Glaucia Aparecida Bento dos Santos, Raquel M. Santos, Lays M. Oliveira, Carlos Augusto Pasqualucci, Wilson Jacob-Filho, and Renata Elaine Paraizo Leite
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Olfactory system ,Male ,Physiology ,lcsh:Medicine ,Functional impact ,Cell Count ,Biology ,Biochemistry ,Pheromones ,Sex Pheromones ,Sex Factors ,Morphogenesis ,Psychology ,Humans ,lcsh:Science ,Aged ,Aged, 80 and over ,Neurons ,Behavior ,Sex Characteristics ,Multidisciplinary ,Sexual Differentiation ,Absolute number ,Neurogenesis ,Significant difference ,lcsh:R ,Biology and Life Sciences ,Brain ,Anatomy ,Organ Size ,Middle Aged ,Olfactory Bulb ,Sensory Systems ,Olfactory bulb ,Sexual dimorphism ,Female ,lcsh:Q ,Human Sexual Behavior ,Neuroglia ,Research Article ,Developmental Biology ,Neuroscience - Abstract
Sex differences in the human olfactory function reportedly exist for olfactory sensitivity, odorant identification and memory, and tasks in which odors are rated based on psychological features such as familiarity, intensity, pleasantness, and others. Which might be the neural bases for these behavioral differences? The number of cells in olfactory regions, and especially the number of neurons, may represent a more accurate indicator of the neural machinery than volume or weight, but besides gross volume measures of the human olfactory bulb, no systematic study of sex differences in the absolute number of cells has yet been undertaken. In this work, we investigate a possible sexual dimorphism in the olfactory bulb, by quantifying postmortem material from 7 men and 11 women (ages 55–94 years) with the isotropic fractionator, an unbiased and accurate method to estimate absolute cell numbers in brain regions. Female bulbs weighed 0.132 g in average, while male bulbs weighed 0.137 g, a non-significant difference; however, the total number of cells was 16.2 million in females, and 9.2 million in males, a significant difference of 43.2%. The number of neurons in females reached 6.9 million, being no more than 3.5 million in males, a difference of 49.3%. The number of non-neuronal cells also proved higher in women than in men: 9.3 million and 5.7 million, respectively, a significant difference of 38.7%. The same differences remained when corrected for mass. Results demonstrate a sex-related difference in the absolute number of total, neuronal and non-neuronal cells, favoring women by 40–50%. It is conceivable that these differences in quantitative cellularity may have functional impact, albeit difficult to infer how exactly this would be, without knowing the specific circuits cells make. However, the reported advantage of women as compared to men may stimulate future work on sex dimorphism of synaptic microcircuitry in the olfactory bulb.
- Published
- 2014
6. Specific cortical and subcortical grey matter regions are associated with insomnia severity.
- Author
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Neus Falgàs, Ignacio Illán-Gala, Isabel E Allen, Paige Mumford, Youssef M Essanaa, Michael M Le, Michelle You, Lea T Grinberg, Howard J Rosen, Thomas C Neylan, Joel H Kramer, and Christine M Walsh
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Medicine ,Science - Abstract
BackgroundThere is an increasing awareness that sleep disturbances are a risk factor for dementia. Prior case-control studies suggested that brain grey matter (GM) changes involving cortical (i.e, prefrontal areas) and subcortical structures (i.e, putamen, thalamus) could be associated with insomnia status. However, it remains unclear whether there is a gradient association between these regions and the severity of insomnia in older adults who could be at risk for dementia. Since depressive symptoms and sleep apnea can both feature insomnia-related factors, can impact brain health and are frequently present in older populations, it is important to include them when studying insomnia. Therefore, our goal was to investigate GM changes associated with insomnia severity in a cohort of healthy older adults, taking into account the potential effect of depression and sleep apnea as well. We hypothesized that insomnia severity is correlated with 1) cortical regions responsible for regulation of sleep and emotion, such as the orbitofrontal cortex and, 2) subcortical regions, such as the putamen.Methods120 healthy subjects (age 74.8±5.7 years old, 55.7% female) were recruited from the Hillblom Healthy Aging Network at the Memory and Aging Center, UCSF. All participants were determined to be cognitively healthy following a neurological evaluation, neuropsychological assessment and informant interview. Participants had a 3T brain MRI and completed the Insomnia Severity Index (ISI), Geriatric Depression Scale (GDS) and Berlin Sleep Questionnaire (BA) to assess sleep apnea. Cortical thickness (CTh) and subcortical volumes were obtained by the CAT12 toolbox within SPM12. We studied the correlation of CTh and subcortical volumes with ISI using multiple regressions adjusted by age, sex, handedness and MRI scan type. Additional models adjusting by GDS and BA were also performed.ResultsISI and GDS were predominantly mild (4.9±4.2 and 2.5±2.9, respectively) and BA was mostly low risk (80%). Higher ISI correlated with lower CTh of the right orbitofrontal, right superior and caudal middle frontal areas, right temporo-parietal junction and left anterior cingulate cortex (pConclusionsOur findings highlight a relationship between insomnia severity and brain health, even with relatively mild insomnia, and independent of depression and likelihood of sleep apnea. The results extend the previous literature showing the association of specific GM areas (i.e, orbitofrontal, insular and temporo-parietal junction) not just with the presence of insomnia, but across the spectrum of severity itself. Moreover, our results suggest subcortical structures (i.e., putamen) are involved as well. Longitudinal studies are needed to clarify how these insomnia-related brain changes in healthy subjects align with an increased risk of dementia.
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- 2021
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- View/download PDF
7. Neuropathological diagnoses and clinical correlates in older adults in Brazil: A cross-sectional study.
- Author
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Claudia K Suemoto, Renata E L Ferretti-Rebustini, Roberta D Rodriguez, Renata E P Leite, Luciana Soterio, Sonia M D Brucki, Raphael R Spera, Tarcila M Cippiciani, Jose M Farfel, Alexandre Chiavegatto Filho, Michel Satya Naslavsky, Mayana Zatz, Carlos A Pasqualucci, Wilson Jacob-Filho, Ricardo Nitrini, and Lea T Grinberg
- Subjects
Medicine - Abstract
BACKGROUND:Clinicopathological studies are important in determining the brain lesions underlying dementia. Although almost 60% of individuals with dementia live in developing countries, few clinicopathological studies focus on these individuals. We investigated the frequency of neurodegenerative and vascular-related neuropathological lesions in 1,092 Brazilian admixed older adults, their correlation with cognitive and neuropsychiatric symptoms, and the accuracy of dementia subtype diagnosis. METHODS AND FINDINGS:In this cross-sectional study, we describe clinical and neuropathological variables related to cognitive impairment in 1,092 participants (mean age = 74 y, 49% male, 69% white, and mean education = 4 y). Cognitive function was investigated using the Clinical Dementia Rating (CDR) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE); neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory (NPI). Associations between neuropathological lesions and cognitive impairment were investigated using ordinal logistic regression. We developed a neuropathological comorbidity (NPC) score and compared it to CDR, IQCODE, and NPI scores. We also described and compared the frequency of neuropathological diagnosis to clinical diagnosis of dementia subtype. Forty-four percent of the sample met criteria for neuropathological diagnosis. Among these participants, 50% had neuropathological diagnoses of Alzheimer disease (AD), and 35% of vascular dementia (VaD). Neurofibrillary tangles (NFTs), hippocampal sclerosis, lacunar infarcts, hyaline atherosclerosis, siderocalcinosis, and Lewy body disease were independently associated with cognitive impairment. Higher NPC scores were associated with worse scores in the CDR sum of boxes (β = 1.33, 95% CI 1.20-1.46), IQCODE (β = 0.14, 95% CI 0.13-0.16), and NPI (β = 1.74, 95% CI = 1.33-2.16). Compared to neuropathological diagnoses, clinical diagnosis had high sensitivity to AD and high specificity to dementia with Lewy body/Parkinson dementia. The major limitation of our study is the lack of clinical follow-up of participants during life. CONCLUSIONS:NFT deposition, vascular lesions, and high NPC scorewere associated with cognitive impairment in a unique Brazilian sample with low education. Our results confirm the high prevalence of neuropathological diagnosis in older adults and the mismatch between clinical and neuropathological diagnoses.
- Published
- 2017
- Full Text
- View/download PDF
8. Morphometric measurements of systemic atherosclerosis and visceral fat: Evidence from an autopsy study.
- Author
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Aline Nishizawa, Claudia K Suemoto, Daniela S Farias-Itao, Fernanda M Campos, Karen C S Silva, Marcio S Bittencourt, Lea T Grinberg, Renata E P Leite, Renata E L Ferretti-Rebustini, Jose M Farfel, Wilson Jacob-Filho, and Carlos A Pasqualucci
- Subjects
Medicine ,Science - Abstract
BACKGROUND:Morphometric measurements of systemic atherosclerosis and direct quantification of visceral fat are only possible using materials from autopsy studies. However, the few autopsy studies that have investigated the association of visceral fat with atherosclerosis had small sample sizes and focused on coronary arteries of young or middle-aged White subjects. We aimed to investigate the association of pericardial fat (PF) and abdominal visceral fat (AVF) with atherosclerosis in the aorta, coronary, carotid, and cerebral arteries in a large autopsy study. MATERIALS AND METHODS:We evaluated deceased subjects aged 30 years or above. We dissected and weighted the PF and the AVF and evaluated the atherosclerotic burden in the aorta, as well as the carotid, coronary, and cerebral arteries using morphometric measurements. We also investigated the interaction of PF and AVF with age regarding the atherosclerotic burden. RESULTS:The mean age of the 240 included subjects was 64.8±15.3 years, and 63% was male. Greater PF was associated with a higher degree of aortic atherosclerosis after adjusting for confounding variables (coefficient = 4.39, 95% CI = 0.83; 7.94, p = 0.02). Greater AVF was associated with a higher coronary stenosis index (coefficient = 1.49, 95% CI = 0.15; 2.83, p = 0.03) and a greater number of coronary plaques (coefficient = 0.71, 95% CI = 0.24; 1.19, p = 0.003). We did not find an association of PF or AVF with carotid or cerebral atherosclerotic burden. We found a significant interaction of AVF (coefficient = -0.08; 95% CI = -0.14; -0.02, p = 0.009) and PF (coefficient = -0.87, 95% CI = -1.70; -0.04, p = 0.04) with age regarding carotid artery atherosclerotic burden. CONCLUSIONS:Greater AVF was associated with greater atherosclerotic burden and extent in coronary arteries, while greater PF correlated with a higher degree of atherosclerosis in the aorta.
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- 2017
- Full Text
- View/download PDF
9. Repair of oxidative DNA damage, cell-cycle regulation and neuronal death may influence the clinical manifestation of Alzheimer's disease.
- Author
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Aderbal R T Silva, Ana Cecília Feio Santos, Jose M Farfel, Lea T Grinberg, Renata E L Ferretti, Antonio Hugo Jose Froes Marques Campos, Isabela Werneck Cunha, Maria Dirlei Begnami, Rafael M Rocha, Dirce M Carraro, Carlos Alberto de Bragança Pereira, Wilson Jacob-Filho, and Helena Brentani
- Subjects
Medicine ,Science - Abstract
Alzheimer's disease (AD) is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles). Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p27Kip1, phospho-Rb and E2F1) through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA) composed of three groups: I) "clinical-pathological AD" (CP-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and clinical dementia (CDR ≥ 2, IQCODE>3.8); II) "pathological AD" (P-AD)--subjects with neuropathological AD (Braak ≥ IV and CERAD = B or C) and without cognitive impairment (CDR 0, IQCODE
- Published
- 2014
- Full Text
- View/download PDF
10. Transcriptional alterations related to neuropathology and clinical manifestation of Alzheimer's disease.
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Aderbal R T Silva, Lea T Grinberg, Jose M Farfel, Breno S Diniz, Leandro A Lima, Paulo J S Silva, Renata E L Ferretti, Rafael M Rocha, Wilson Jacob Filho, Dirce M Carraro, and Helena Brentani
- Subjects
Medicine ,Science - Abstract
Alzheimer's disease (AD) is the most common cause of dementia in the human population, characterized by a spectrum of neuropathological abnormalities that results in memory impairment and loss of other cognitive processes as well as the presence of non-cognitive symptoms. Transcriptomic analyses provide an important approach to elucidating the pathogenesis of complex diseases like AD, helping to figure out both pre-clinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. This study provides the gene expression profile of postmortem brain tissue from subjects with clinic-pathological AD (Braak IV, V, or V and CERAD B or C; and CDR ≥1), preclinical AD (Braak IV, V, or VI and CERAD B or C; and CDR = 0), and healthy older individuals (Braak ≤ II and CERAD 0 or A; and CDR = 0) in order to establish genes related to both AD neuropathology and clinical emergence of dementia. Based on differential gene expression, hierarchical clustering and network analysis, genes involved in energy metabolism, oxidative stress, DNA damage/repair, senescence, and transcriptional regulation were implicated with the neuropathology of AD; a transcriptional profile related to clinical manifestation of AD could not be detected with reliability using differential gene expression analysis, although genes involved in synaptic plasticity, and cell cycle seems to have a role revealed by gene classifier. In conclusion, the present data suggest gene expression profile changes secondary to the development of AD-related pathology and some genes that appear to be related to the clinical manifestation of dementia in subjects with significant AD pathology, making necessary further investigations to better understand these transcriptional findings on the pathogenesis and clinical emergence of AD.
- Published
- 2012
- Full Text
- View/download PDF
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