Biology subjects

Keator, D. B.

Publications and source records attributed to Keator, D. B..

3 recordsLinked to original sources

bioRxiv2022

Entorhinal-hippocampal circuit integrity is related to mnemonic discrimination and amyloid-β pathology in older adults

Mnemonic discrimination, a cognitive process that relies on hippocampal pattern separation, is one of the first memory domains to decline in aging and preclinical Alzheimers disease. We tested if functional connectivity (FC) within the entorhinal-hippocampal circuit, measured with high-resolution resting state fMRI, is associated with mnemonic discrimination and A{beta} pathology, measured with PET, in nondemented older adults. Low object mnemonic discrimination performance was specifically associated with increased FC between anterolateral entorhinal cortex (alEC) and dentate gyrus (DG)/CA3, supporting the importance of this connection to object memory. This hyperconnectivity between alEC-DG/CA3 was related to A{beta} pathology and decreased entorhinal cortex volume. In contrast, spatial mnemonic discrimination was not associated with altered FC. A{beta} was further associated with decreased FC and volume within hippocampal subfields. Our findings suggest that A{beta} may indirectly lead to memory impairment through entorhinal-hippocampal circuit dysfunction and neurodegeneration, and provide a mechanism for vulnerability of object mnemonic discrimination.

neuroscience↗

bioRxiv2020

Brain Amyloid and the Transition to Dementia in Down Syndrome

INTRODUCTIONDown syndrome (DS) is associated with elevated risk for Alzheimers disease (AD) due to beta amyloid (A{beta}) lifelong accumulation. We hypothesized that the spatial distribution of brain A{beta} predicts future dementia conversion in individuals with DS. METHODSWe acquired 18F-Florbetapir PET scans from 19 nondemented individuals with DS at baseline and monitored them for four years, with five individuals transitioning to dementia. Machine learning classification determined features on 18F-Florbetapir standardized uptake value ratio (SUVR) maps that predicted transition. RESULTSIn addition to "AD signature" regions including the inferior parietal cortex, temporal lobes, and the cingulum, we found that A{beta} cortical binding in the prefrontal and superior frontal cortices distinguished subjects who transitioned to dementia. Classification did well in predicting transitioners. DISCUSSIONOur study suggests that specific regional profiles of brain amyloid in older adults with DS may predict cognitive decline and are informative in evaluating the risk for dementia. HighlightsO_LIRegional [18F]-Florbetapir PET predicts future transition to dementia in Downs Syndrome. C_LIO_LIIncreased amyloid in prefrontal, inferior parietal, superior frontal, rostral middle frontal, and posterior cingulate cortices detect transitioiners, with prefrontal and superior frontal being best overall. C_LIO_LIAmyloid PET-based classification able to discriminate between transitioners and non-transitioners. C_LI

neuroscience↗

bioRxiv2018

-Florbetapir PET: Towards Predicting Dementia in Adults with Down Syndrome

1. Background 1. Background 2. Methods 3. Results 4. Discussion 5. Conclusions References Individuals with Down syndrome (DS) have an increasing age-related prevalence of Alzheimers disease (AD). In DS, the triplication of amyloid precursor protein (APP) on chromosome 21 contributes to a life-long accumulation of brain amyloid (A{beta}) [1]. Dyshomeostasis of A{beta} has emerged as one of the most well-validated factors in the pathogenesis of AD [2]. By age 40 years, virtually all individuals with DS have amyloid plaques and tau tangles, hallmark pathologies that are characteristic of sporadic AD in the general population [3]. Dementia, while not inevitable in DS, increases significantly in prevalence with age to over 75% after age 65 years. [ ...

neuroscience↗