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
Date Published2017 Mar
KeywordsAdult, Aged, Aged, 80 and over, Alzheimer Disease, Autopsy, Biomarkers, Disease Progression, Female, Humans, Locus Coeruleus, Male, Middle Aged, Neurons, Stereotaxic Techniques

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.

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