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Neuronal Hypertrophy in Asymptomatic Alzheimer Disease
Open accessAbstract
The pathologic changes of Alzheimer disease (AD) evolve very gradually over decades before the disease becomes clinically manifest. Thus, it is not uncommon to find substantial numbers of Abeta plaques and neurofibrillary tangles in autopsy brains of older subjects with documented normal cognition, a state that we define as asymptomatic AD (ASYMAD). The goal of this study is to understand the morphometric substrate of ASYMAD subjects compared with mild cognitive impairment and definite AD cases. We used designed-based stereology to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in 4 cerebral regions: anterior cingulate gyrus, posterior cingulate gyrus, primary visual cortex, and CA1 of hippocampus. We examined and compared autopsy brains from 4 groups (n = 15 each) of participants in the Baltimore Longitudinal Study of Aging: ASYMAD, mild cognitive impairment, AD, and age-matched controls. We found significant hypertrophy of the neuronal cell bodies, nuclei, and nucleoli of CA1 of hippocampus and anterior cingulate gyrus neurons in ASYMAD subjects compared with control and mild cognitive impairment cases. In the posterior cingulate gyrus and primary visual cortex, the hypertrophy was limited to the nuclei and nucleoli. The hypertrophy of cortical neurons and their nuclei and nucleoli in ASYMAD may represent an early reaction to the presence of neurotoxic Abeta or tau, or a compensatory mechanism that prevents the progression of the disease into dementia.
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“These individuals have neuritic plaque and NFTs Braak stages at autopsy comparable to those of AD subjects with dementia, and the literature refers to them as resilient [31], Nondemented with AD Neuropathology (NDAN) [83], or asymptomatic AD (AsymAD) [22, 42].”
From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [42]
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“studies have demonstrated that AsymAD brains exhibit no signs of notorious synaptic or neuronal deterioration [8, 42, 73]”
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Metadata
- Authors
- Iacono, D., O'Brien, R., Resnick, S. M., Zonderman, A. B., Pletnikova, O., Rudow, G., An, Y., West, M. J., Crain, B., & Troncoso, J. C.
- Affiliations
- Johns Hopkins University (US)
- National Institutes of Health (US)
- Aarhus University (DK)
- Corresponding author
- Troncoso, Juan C.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-06
- Volume
- 67
- Issue
- 6
- Pages
- 578-589
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC2518071
- OpenAlex
- W2097399504
- Cited by
- 188
- References
- 67
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 15 · 2023: 7 · 2022: 11 · 2021: 12 · 2020: 6 · 2019: 14 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 10 · 2014: 13 · 2013: 17 · 2012: 8
- FWCI
- 6.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Burroughs Wellcome Fund
- Johns Hopkins University
- National Institutes of Health
- National Institute on Aging (K23AG034550, Z01AG000191, P50AG005146, AG 05146)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- neuronal hypertrophy, hippocampal CA1, anterior cingulate cortex, posterior cingulate cortex, primary visual cortex, mild cognitive impairment, amyloid plaques, neurofibrillary tangles, stereology
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition Disorders, Humans, Hypertrophy, Neurons
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