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

• DOI: 10.1016/j.jalz.2016.06.2362
• Publication Date: 2016-08-09T19:08:34Z
• Authors: Panos Theofilas; Alexander J. Ehre...; Sara Dunlop; Ana T. Di Lorenzo...; Austin Nguy; Renata Elaine Par...; Roberta Diehl Rod...; Maria B. Mejia; Claudia K. Suemoto; Renata Eloah De L...; Livia Polichiso; Camila F. Nascimento; William W. Seeley; Ricardo Nitrini; Carlos Augusto Pa...; Wilson Jacob Filho; Udo Rueb; John Neuhaus; Helmut Heinsen; Lea T. Grinberg
• Keywords: Unbiased stereology; Male; Aging; Biological Psychology; Clinical sciences; Neurodegenerative; Alzheimer's Disease; Stereotaxic Techniques; Volumetry; 0302 clinical medicine; 80 and over; Locus coeruleus; Psychology; Aged, 80 and over; Neurons; screening and diagnosis; Alzheimer's disease; Middle Aged; 3. Good health; Detection; Neurological; Disease Progression; Female; Locus Coeruleus; Neuron counts; Autopsy; Brainstem; Human; Neurofibrillary tangles; Adult; Clinical Sciences; 610; Bioengineering; 03 medical and health sciences; Alzheimer Disease; Acquired Cognitive Impairment; Humans; Aged; Biomedical and Clinical Sciences; Prevention; Neurosciences; Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD); 4.1 Discovery and preclinical testing of markers and technologies; Brain Disorders; Postmortem; Geriatrics; Biological psychology; Dementia; Biomarkers

AbstractIntroductionAlzheimer'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]).MethodsThe methods include unbiased stereological analyses in human brainstems to estimate LC volume and neuronal population in controls and individuals across all AD stages.ResultsAs 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.DiscussionThe 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.