Locus 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

• Published in: Alzheimer's & dementia Vol. 13; no. 3; pp. 236 - 246
• Main Authors: Theofilas, Panos, Ehrenberg, Alexander J, Dunlop, Sara, Di Lorenzo Alho, Ana T, Nguy, Austin, Leite, Renata Elaine Paraizo, Rodriguez, Roberta Diehl, Mejia, Maria B, Suemoto, Claudia K, Ferretti-Rebustini, Renata Eloah De Lucena, Polichiso, Livia, Nascimento, Camila F, Seeley, William W, Nitrini, Ricardo, Pasqualucci, Carlos Augusto, Jacob Filho, Wilson, Rueb, Udo, Neuhaus, John, Heinsen, Helmut, Grinberg, Lea T
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2017
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease - pathology; Alzheimer's disease; Autopsy; Biomarkers - metabolism; Brainstem; Disease Progression; Female; Human; Humans; Locus coeruleus; Locus Coeruleus - pathology; Male; Middle Aged; Neurofibrillary tangles; Neurology; Neuron counts; Neurons - pathology; Postmortem; Stereotaxic Techniques; Unbiased stereology; Volumetry; Human; Neurofibrillary tangles; Neuron counts; Volumetry; Brainstem; Postmortem; Alzheimer's disease; Locus coeruleus; Unbiased stereology
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1016/j.jalz.2016.06.2362

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.