Dataset Information

Metabolic Syndrome and Amyloid Accumulation in the Aging Brain.

ABSTRACT: BACKGROUND:Recent studies show links between metabolic syndrome and Alzheimer's disease (AD) neuropathology. Understanding the link between vascular-related health conditions and dementia will help target at risk populations and inform clinical strategies for early detection and prevention of AD. OBJECTIVE:To determine whether metabolic syndrome is associated with global cerebral amyloid-? (A?) positivity and longitudinal A? accumulation. METHODS:Prospective study of 165 participants who underwent (11)C-Pittsburgh compound B (PiB) PET neuroimaging to measure A?, from June 2005 to May 2016. Metabolic syndrome was defined using the revised Third Adults Treatment Panel of the National Cholesterol Education Program criteria. Participants were classified as PiB+/-. Linear mixed effects models assessed the relationships between baseline metabolic syndrome and PiB status and regional A? change over time. RESULTS:A total of 165 cognitively normal participants of the Baltimore Longitudinal Study of Aging (BLSA) Neuroimaging substudy, aged 55-92 years (mean baseline age?=?76.4 years, 85 participants were male), received an average of 2.5 PET-PiB scans over an average interval of 2.6 (3.08 SD) years between first and last visits. Metabolic syndrome was not associated with baseline PiB positivity or concurrent regional A?. Metabolic syndrome was associated with increased rates of A? accumulation in superior parietal and precuneus regions over time in the PiB+ group. Elevated fasting glucose and blood pressure showed individual associations with accelerated A? accumulation. CONCLUSION:Metabolic syndrome was associated with accelerated A? accumulation in PiB+ individuals and may be an important factor in the progression of AD pathology.

SUBMITTER: Gomez G

PROVIDER: S-EPMC6176485 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Metabolic Syndrome and Amyloid Accumulation in the Aging Brain.

Gomez Gabriela G Beason-Held Lori L LL Bilgel Murat M An Yang Y Wong Dean F DF Studenski Stephanie S Ferrucci Luigi L Resnick Susan M SM

Journal of Alzheimer's disease : JAD 20180101 2

<h4>Background</h4>Recent studies show links between metabolic syndrome and Alzheimer's disease (AD) neuropathology. Understanding the link between vascular-related health conditions and dementia will help target at risk populations and inform clinical strategies for early detection and prevention of AD.<h4>Objective</h4>To determine whether metabolic syndrome is associated with global cerebral amyloid-β (Aβ) positivity and longitudinal Aβ accumulation.<h4>Methods</h4>Prospective study of 165 pa ...[more]

PMID: 30103324

Similar Datasets

Project description:BackgroundThe role of mitochondrial dysfunction has long been implicated in age-related brain pathology, including Alzheimer's disease (AD). However, the mechanism by which mitochondrial dysfunction may cause neurodegeneration in AD is unclear. To model mitochondrial dysfunction in vivo, we utilized mice that harbor a knockin mutation that inactivates the proofreading function of mitochondrial DNA polymerase ? (PolgA D257A), so that these mice accumulate mitochondrial DNA mutations with age. PolgA D257A mice develop a myriad of mitochondrial bioenergetic defects and physical phenotypes that mimic premature ageing, with subsequent death around one year of age.ResultsWe crossed the D257A mice with a well-established transgenic AD mouse model (APP/Ld) that develops amyloid plaques. We hypothesized that mitochondrial dysfunction would affect A? synthesis and/or clearance, thus contributing to amyloidogenesis and triggering neurodegeneration. Initially, we discovered that A?42 levels along with A?42 plaque density were increased in D257A; APP/Ld bigenic mice compared to APP/Ld monogenic mice. Elevated A? production was not responsible for increased amyloid pathology, as levels of BACE1, PS1, C99, and C83 were unchanged in D257A; APP/Ld compared to APP/Ld mice. However, the levels of a major A? clearance enzyme, insulin degrading enzyme (IDE), were reduced in mice with the D257A mutation, suggesting this as mechanism for increased amyloid load. In the presence of the APP transgene, D257A mice also exhibited significant brain atrophy with apparent cortical thinning but no frank neuron loss. D257A; APP/Ld mice had increased levels of 17 kDa cleaved caspase-3 and p25, both indicative of neurodegeneration. Moreover, D257A; APP/Ld neurons appeared morphologically disrupted, with swollen and vacuolated nuclei.ConclusionsOverall, our results implicate synergism between the effects of the PolgA D257A mutation and A? in causing neurodegeneration. These findings provide insight into mechanisms of mitochondrial dysfunction that may contribute to the pathogenesis of AD via decreased clearance of A?.

Dataset Information

Metabolic Syndrome and Amyloid Accumulation in the Aging Brain.

Publications

Metabolic Syndrome and Amyloid Accumulation in the Aging Brain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets