Search

Background: Cholesterol homeostasis dysfunction has been reported to have role in the pathogenesis of Alzheimer disease (AD). Therefore, changes in cholesterol metabolism in blood components may help to develop new potential AD biomarkers. In this study changes in cholesterol metabolism-related gene expression genes were evaluated in peripheral blood mononuclear cells (PBMCs) from AD subjects, their first degree relatives (FDR) and two groups of age matched controls (C1 > 80 years, C2 < 60 years). The expression of three genes related to APP processing was also determined., Results: Results showed significantly different behavior (P = 0.000) in the expression of all analyzed genes among the 4 groups. An inverse correlation emerged between the age of controls and the propensity of their PBMCs to express selected genes. Moreover, when gene expression was evaluated in PBMCs from AD patients and compared with that of PBMCs from healthy subjects of the same age, LDL-R and APP mRNAs were most abundant in AD as compared C1 whereas SREBP-2 and particularly nCEH were present at much lower mRNA levels in AD-PBMCs. This study describes for the first time a differential expression profile of cholesterol and APP related genes in PBMCs from AD patients and their FDR., Conclusions: We suggest that the expressions of cholesterol homeostasis and APP processing related genes in PBMC could be proposed as possible biomarkers to evaluate AD risk. In addition, gene expression in PBMC could be also used for diagnosis and development of therapeutic strategies as well as for personalized prediction in clinical outcome of AD.

Objectives: Analysis of variations of nutritional status in relation to psycho-functional conditions in elderly patients with mild to moderate Alzheimer's disease (AD) by means of bioelectrical impedance vector analysis (BIVA)., Design: Cross-sectional study., Setting: Alzheimer Center, SS. Trinità Hospital, Cagliari (Italy)., Participants: 83 free-living patients (29 men, 54 women) with mild-moderate Alzheimer's disease, aged 66 to 96 years, and 91 age-matched controls (37 men and 54 women)., Measurements: Nutritional status was evaluated by anthropometry (weight, height, waist and upper arm circumferences, triceps skinfold; body mass index, BMI; arm muscle area, AMA); Mini Nutritional Assessment, MNA®; bioelectrical impedance vector analysis, BIVA. Psycho-functional status was assessed by the Mini Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL)., Results: Compared to the control groups, patients with Alzheimer's disease had a worse psycho-functional and nutritional status. BIVA detected lower body cell mass in Alzheimer's patients with respect to controls (men: T²= 23.4; women: T²=27.3; p<0.01), as well as in the female patients with lower levels of IADL and MMSE (respectively, T²= 8.0; T²=7.4; p<0.05). In patients with AD, a worse psycho-functional status was associated with obesity., Conclusion: The psycho-functional decline of patients with AD is related to body composition variations, with a relative increase of fat mass with respect to the muscle component. The BIVA technique distinguished patients from controls and patients with different levels of cognitive decline. Therefore, it is a suitable tool for the screening and monitoring of nutritional status in Alzheimer's disease.

Objectives: This paper evaluates the nutritional status in patients with mild-moderate and severe Alzheimer's disease (AD) by bioelectrical impedance vector analysis (BIVA)., Design: Cross-sectional study., Setting: Alzheimer Center, SS. Trinita Hospital, Cagliari, and "Monsignor Angioni" Nursing Home, Quartu Sant'Elena (Cagliari, Italy)., Participants: 83 free-living patients with mild-moderate Alzheimer's disease (29 men, 54 women), 9 institutionalized women in the severe stage; 468 age-matched controls (202 men, 266 women)., Measurements: Mini Nutritional Assessment (MNA), anthropometric (height, weight, BMI), bioelectrical (R, Xc) and biochemical variables (serum albumin) were assessed., Results: Bioelectrical characteristics were significantly different in the patients with mild-moderate AD with respect to controls, indicating low body cell mass (men, T2= 12.8; women, T2=34.9; p < 0.01). Women with severe AD showed low body cell mass and dehydration with respect to patients with mild-moderate AD (T2=17.1; p < 0.01). The phase angle, R/H and Z/H were significantly correlated (p < 0.05) with MNA (phase: r = 0.31; R/H: r =-0.37; Z/H: r =-0.37) and albumin (phase: r=0.47; R/H: r=-0.36; Z/H: r=-0.36)., Conclusion: Alzheimer's disease is characterized by a tendency to malnutrition, present even in the mild-moderate stages, and a tendency to dehydration that appears in the severe stage. The BIVA technique is a promising tool for the screening and monitoring of nutrition and hydration status in Alzheimer's disease.

Background: Alzheimer's disease is the most common progressive neurodegenerative disease. In recent years, numerous progresses in the discovery of novel Alzheimer's disease molecular biomarkers in brain as well as in biological fluids have been made. Among them, those involving lipid metabolism are emerging as potential candidates. In particular, an accumulation of neutral lipids was recently found by us in skin fibroblasts from Alzheimer's disease patients. Therefore, with the aim to assess whether peripheral alterations in cholesterol homeostasis might be relevant in Alzheimer's disease development and progression, in the present study we analyzed lipid metabolism in plasma and peripheral blood mononuclear cells from Alzheimer's disease patients and from their first-degree relatives., Methods: Blood samples were obtained from 93 patients with probable Alzheimer's disease and from 91 of their first-degree relatives. As controls we utilized 57, cognitively normal, over-65 year-old volunteers and 113 blood donors aged 21-66 years, respectively. Data are reported as mean +/- standard error. Statistical calculations were performed using the statistical analysis software Origin 8.0 version. Data analysis was done using the Student t-test and the Pearson test., Results: Data reported here show high neutral lipid levels and increased ACAT-1 protein in about 85% of peripheral blood mononuclear cells freshly isolated (ex vivo) from patients with probable sporadic Alzheimer's disease compared to about 7% of cognitively normal age-matched controls. A significant reduction in high density lipoprotein-cholesterol levels in plasma from Alzheimer's disease blood samples was also observed. Additionally, correlation analyses reveal a negative correlation between high density lipoprotein-cholesterol and cognitive capacity, as determined by Mini Mental State Examination, as well as between high density lipoprotein-cholesterol and neutral lipid accumulation. We observed great variability in the neutral lipid-peripheral blood mononuclear cells data and in plasma lipid analysis of the subjects enrolled as Alzheimer's disease-first-degree relatives. However, about 30% of them tend to display a peripheral metabolic cholesterol pattern similar to that exhibited by Alzheimer's disease patients., Conclusion: We suggest that neutral lipid-peripheral blood mononuclear cells and plasma high density lipoprotein-cholesterol determinations might be of interest to outline a distinctive metabolic profile applying to both Alzheimer's disease patients and asymptomatic subjects at higher risk of disease.

Alzheimer's disease (AD) is characterized by an extensive loss of cholinergic neurons, and their cortical projections, from the basal forebrain area. The resulting reduction in cholinergic activity is associated with decreased levels of the neurotransmitter acetylcholine (ACh), decreased activity of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and increased butyrylcholinesterase (BChE) activity. In the present study, we investigated whether the BCHE, ACHE, and CHAT genes were associated with AD and the possibility of a synergistic effect with APOE-epsilon4 in a Sardinian sample. AD patients (n = 158), exclusively of Sardinian ancestry, were recruited from the Division of Geriatrics Local Health Agency 8 and Unit of Clinical Pharmacology, Department of Neurosciences, University of Cagliari. Patients were diagnosed according to DSM-IV, and National Institute of Neurologic and Communicative Disorders and Stroke-AD and Related Disorders Association (NINCDS-ADRDA) criteria for possible or probable AD. Cognitive screening was performed by means of Mini-Mental State Examination (MMSE). Healthy controls (n = 118) of Sardinian ancestry were recruited from religious and sport associations. All patients and control subjects gave informed consent for participation in the study. Single nucleotide polymorphism (SNP) analysis was performed by PCR/RFLP or the TaqMan 5' exonuclease method. Our study confirms the association between APOE epsilon4 allele and AD (P < 0.000). No significant differences were observed in allele and genotype frequencies of BCHE, ACHE, and CHAT between AD and controls. Haplotype analysis of ACHE SNPs did not reveal a significant association between ACHE and AD. Our results suggest that the AChE, ChAT, and BChE polymorphisms do not constitute a major genetic risk factor for susceptibility to AD in a Sardinian population., ((c) 2007 Wiley-Liss, Inc.)

Background: The clinical picture of Alzheimer's disease includes anthropometric and body composition variations. Somatotyping is a practical non-invasive method to assess body type., Objective: The objective of this study was to describe the somatotype of a sample of Alzheimer's patients., Methods: The sample consisted of 55 Alzheimer disease individuals in the mild-moderate stage (17 men, mean age = 76.9 +/- 7.2 years; 38 women, mean age = 79.6 +/- 6.4 years). The pathological subjects were compared with a control group consisting of 280 healthy individuals (134 men, mean age = 74.2 +/- 7.3 years; 146 women, mean age = 74.9 +/- 7.4 years). The Heath-Carter somatotype was applied., Results: The Alzheimer patients (mean somatotype: 6.1-5.5-0.8 in men, 7.0-5.3-0.7 in women) are less mesomorphic and more ectomorphic than the controls (mean somatotype: 6.1-6.3-0.6 in men, 7.7-6.3-0.4 in women), the differences being significant in women (mesomorphy, p = 0.000; ectomorphy, p = 0.012)., Conclusion: Alzheimer patients show peculiar somatometric characteristics. The somatotype technique could represent a suitable tool for the study and monitoring of physical variations., (Copyright 2007 S. Karger AG, Basel.)

We report on a case of reversible Pisa syndrome developed after treatment with galantamine in a patient with Alzheimer's disease without previous exposure to neuroleptic or other cholinesterase inhibitors. Complete and persistent resolution of the syndrome was achieved several weeks after botulinum toxin type-A injection., ((c) 2004 Movement Disorder Society.)