TitleLocus coeruleus volume and cell population changes during Alzheimer's disease progression: A stereological study in human postmortem brains with potential implication for early-stage biomarker discovery.
Publication TypeJournal Article
Year of Publication2017
AuthorsTheofilas P, Ehrenberg AJ, Dunlop S, Alho ATDi Loren, Nguy A, Leite RElaine Par, Rodriguez RDiehl, Mejia MB, Suemoto CK, Ferretti-Rebustini REloah De L, Polichiso L, Nascimento CF, Seeley WW, Nitrini R, Pasqualucci CAugusto, Filho WJacob, Rueb U, Neuhaus J, Heinsen H, Grinberg LT
JournalAlzheimers Dement
Volume13
Issue3
Pagination236-246
Date Published2017 Mar
ISSN1552-5279
KeywordsAdult, Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Biomarkers, Disease Progression, Female, Humans, Locus Coeruleus, Male, Middle Aged, Neurons, Stereotaxic Techniques
Abstract

INTRODUCTION: Alzheimer's disease (AD) progression follows a specific spreading pattern, emphasizing the need to characterize those brain areas that degenerate first. The brainstem's locus coeruleus (LC) is the first area to develop neurofibrillary changes (neurofibrillary tangles [NFTs]).

METHODS: The methods include unbiased stereological analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages.

RESULTS: As the Braak stage increases by 1 unit, the LC volume decreases by 8.4%. Neuronal loss started only midway through AD progression. Age-related changes spare the LC.

DISCUSSION: The long gap between NFT accumulation and neuronal loss suggests that a second trigger may be necessary to induce neuronal death in AD. Imaging studies should determine whether LC volumetry can replicate the stage-wise atrophy observed here and how these changes are specific to AD. LC volumetry may develop into a screening biomarker for selecting high-yield candidates to undergo expensive and less accessible positron emission tomography scans and to monitor AD progression from presymptomatic stages.

DOI10.1016/j.jalz.2016.06.2362
Alternate JournalAlzheimers Dement
PubMed ID27513978
PubMed Central IDPMC5298942
Grant ListP01 AG019724 / AG / NIA NIH HHS / United States
P50 AG023501 / AG / NIA NIH HHS / United States
R01 AG040311 / AG / NIA NIH HHS / United States