Synapse stability in the precuneus early in the progression of Alzheimer's disease

Document Type

Article

Abstract

Amnestic mild cognitive impairment (aMCI) is considered to be one of the early stages in the progression from no cognitive impairment (NCI) to Alzheimer's disease (AD). Individuals with aMCI have increased levels of AD-type neuropathology in multiple regions of the neocortex and hippocampus and demonstrate a loss of synaptic connectivity. Recent neuroimaging studies have reported increased levels of 11C-PiB (Pittsburgh, compound B) in regions of the neocortex including the precuneus region of the medial parietal lobe. This cortical region has been implicated in episodic memory, which is disrupted early in the progression of AD. In this study, unbiased stereology coupled with electron microscopy was used to quantify total synaptic numbers in lamina 3 of the precuneus from short postmortem autopsy tissue harvested from subjects who died at different cognitive stages during the progression of AD. Individuals with aMCI did not reveal a statistically significant decline in total synapses compared to the NCI cohort while the AD group did show a modest but significant decline. Synaptic numbers failed to correlate with several different cognitive tasks including the Mini-Mental State Examination scores and episodic memory scores. Although levels of [3H]PiB binding were elevated in both the aMCI and AD groups, it did not strongly correlate with synaptic counts. These results support the idea that despite increased amyloid load, the precuneus region does not show early changes in synaptic decline during the progression of AD.

Medical Subject Headings

Aged; Aged, 80 and over; Alzheimer Disease (pathology); Amyloidosis (pathology); Cognitive Dysfunction (pathology); Disease Progression; Female; Hippocampus (pathology); Humans; Male; Memory, Episodic; Mental Status Schedule; Microscopy, Electron; Neocortex (pathology); Neuronal Plasticity (physiology); Neuropsychological Tests; Occipital Lobe (pathology); Parietal Lobe (pathology); Statistics as Topic; Synapses (pathology)

Publication Date

1-1-2013

Publication Title

Journal of Alzheimer's disease : JAD

E-ISSN

1875-8908

Volume

35

Issue

3

First Page

599

Last Page

609

PubMed ID

23478309

Digital Object Identifier (DOI)

10.3233/JAD-122353

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