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. Issue 3 (8th August 2016)

• Record Type: Journal Article
• 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.
• Is Part Of: Alzheimer's & dementia. Volume 13:Issue 3(2017)
• Page Start: 236
• Page End: 246
• Publication Date: 2016-08-08
• Subjects: Alzheimer's disease -- Brainstem -- Locus coeruleus -- Human -- Neurofibrillary tangles -- Unbiased stereology -- Postmortem -- Neuron counts -- Volumetry; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2016.06.2362
• Languages: English
• ISSNs: 1552-5260

Abstract

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.