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Accumulation of aggregated amyloid-β (Aβ) in the brain is considered the first pathological event within the pathogenesis of Alzheimer's disease (AD). It is difficult to accurately identify the initial brain regions of Aβ accumulation due to the time-lag between the start of the pathophysiology and symptom onset. However, focal regional amyloid uptake on amyloid PET scans may provide insights into this. Hence, we aimed to evaluate the topographic distribution of amyloid deposition in patients with cognitive impairment and to identify the starting order of amyloid accumulation in the brain using conditional probability. We enrolled 58 patients composed of 9 normal cognition (NC), 32 mild cognitive impairment (MCI), and 17 dementia showing focal regional amyloid deposition corresponding to a brain amyloid plaque load (BAPL) score of 2 among those who visited the Memory Clinic of Asan Medical Center and underwent an 18F-florbetaben PET scan (March 2013 to April 2019). Regions of interest (ROI) included the frontal, parietal, lateral temporal, and occipital cortices, the posterior cingulate/precuneus, and the striatum. The most frequent occurrence of Aβ deposition was in the posterior cingulate/precuneus (n = 41, 68.3%). The second most frequent site was the lateral temporal cortex (n = 24, 40.0%), followed by the lateral parietal cortex (n = 21, 35.6%) and other lesions, such as the frontal and occipital cortices. The striatum was the least frequently affected. Our study found that the posterior cingulate/precuneus and the lateral temporal and parietal cortices may be the earliest areas to be affected by Aβ accumulation. Longitudinal follow-up of focal brain amyloid deposition may help elucidate the evolutionary pattern of Aβ accumulation in the brain of people with AD continuum. [ABSTRACT FROM AUTHOR]

Background: Around 15% to 20% of patients with clinically probable Alzheimer disease have been found to have no significant Alzheimer pathology on amyloid positron emission tomography. A previous study showed that conversion to dementia from amyloid-negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition.Object: We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid-negative amnestic MCI.Methods: This study was a single-institutional, retrospective cohort study of amyloid-negative MCI patients over age 50 with at least 36 months of follow-up. All subjects underwent detailed neuropsychological testing, 3 tesla brain magnetic resonance imaging), and fluorine-18(18F)-florbetaben amyloid positron emission tomography scans.Results: During the follow-up period, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairment in all visual memory tasks. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole.Conclusion: Our study showed that reduced gray matter volume related to visual memory processing may predict clinical progression in this amyloid-negative MCI population. [ABSTRACT FROM AUTHOR]

Amyloid (Aβ) and tau proteins are pathologic hallmarks of Alzheimer disease (AD). It is well known that there is spatial disparity between Aβ and tau protein deposition but, crossed hemispheric accumulation of these 2 proteins has not been reported. Here we report the case of a 76-year-old woman with typical AD who underwent amyloid positron emission tomography (PET) ([ 18 F]-florbetaben) and tau PET scans ([ 18 F]PI-2620), revealing crossed accumulation of Aβ and tau in the cerebral hemisphere. A neuropsychological assessment showed impairment in memory with spared activities of daily living. In the PET analysis, amyloid deposition was observed only in the left side of the cerebral hemisphere and tau only in the right side. Neuroimaging follow-up indicated that the spatial pattern of these protein accumulations had not changed. This case suggests the possibility of independent Aβ and tau pathogenic pathways in AD. [ABSTRACT FROM AUTHOR]

Microglial activation is a central player in the pathophysiology of Alzheimer's disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD. Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF. In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age. Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

Background and purpose: As part of network‐specific neurodegeneration, changes in cerebellar gray matter (GM) volume and impaired cerebello–cerebral functional networks have been reported in Alzheimer disease (AD). Compared with healthy controls, a volume loss in the cerebellum has been observed in patients with continuum of AD. However, little is known about the anatomical or functional changes in patients with clinical AD but no brain amyloidosis. We aimed to identify the relationship between cerebellar volume and dementia conversion of amyloid‐negative mild cognitive impairment (MCI). Methods: This study was a retrospective cohort study of patients over the age 50 years with amyloid‐negative amnestic MCI who visited the memory clinic of Asan Medical Center with no less than a 36‐month follow‐up period. All subjects underwent detailed neuropsychological tests, 3 T brain magnetic resonance imaging scans including three‐dimensional T1 imaging, and fluorine‐18[F18]‐florbetaben amyloid positron emission tomography scans. A spatially unbiased atlas template of the cerebellum and brainstem was used for analyzing cerebellar GM volume. Results: During the 36 months of follow‐up, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairments in all visual memory tasks. In terms of volumetric analysis, reduced crus I/II volume adjusted with total intracranial volume, and age was observed in the converter group. Conclusions: Significant cerebellar GM atrophy involving the bilateral crus I/II may be a novel imaging biomarker for predicting dementia progression in amyloid‐negative amnestic MCI patients. [ABSTRACT FROM AUTHOR]