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Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer’s pathology
Journal article   Open access   Peer reviewed

Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer’s pathology

Taylor W Schmitz, R Nathan Spreng and Alzheimer's Disease Neuroimaging Initiative
Nature communications, Vol.7(1), pp.13249-13249
11/04/2016
DOI: 10.1038/ncomms13249
PMCID: PMC5097157
PMID: 27811848
url
https://doi.org/10.1038/ncomms13249View
Published (Version of record) Open Access

Abstract

There is considerable debate whether Alzheimer’s disease (AD) originates in basal forebrain or entorhinal cortex. Here we examined whether longitudinal decreases in basal forebrain and entorhinal cortex grey matter volume were interdependent and sequential. In a large cohort of age-matched older adults ranging from cognitively normal to AD, we demonstrate that basal forebrain volume predicts longitudinal entorhinal degeneration. Models of parallel degeneration or entorhinal origin received negligible support. We then integrated volumetric measures with an amyloid biomarker sensitive to pre-symptomatic AD pathology. Comparison between cognitively matched normal adult subgroups, delineated according to the amyloid biomarker, revealed abnormal degeneration in basal forebrain, but not entorhinal cortex. Abnormal degeneration in both basal forebrain and entorhinal cortex was only observed among prodromal (mildly amnestic) individuals. We provide evidence that basal forebrain pathology precedes and predicts both entorhinal pathology and memory impairment, challenging the widely held belief that AD has a cortical origin.

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