Resistance to Alzheimer's pathology is associated with nuclear hypertrophy in neurons
Open accessAbstract
This study focuses on the morphometric changes of neurons in asymptomatic Alzheimer's disease (AD), a state characterized by the presence of AD lesions in subjects without cognitive impairment. In autopsy brains, we used stereological methods to compare the cell body and nuclear volumes of anterior cingulate gyrus (ACG) and CA1 hippocampal neurons in asymptomatic AD subjects (n=9), subjects with AD dementia (AD, n=8), mild cognitive impairment (MCI, n=9), and age-matched controls (controls, n=9). In ACG, we observed a significant decrease in the neuronal volume of MCI and AD compared to controls; by contrast, no atrophy was present in asymptomatic AD. Moreover, we found a significant increase in nuclear volume in asymptomatic AD compared to controls (P<0.001), MCI (P<0.01) and AD (P<0.001) brains. Similar results were found in the CA1 region of the hippocampus. This nuclear hypertrophy may represent an early neuronal reaction to Abeta or Tau, or a compensatory mechanism which forestalls the progression of AD and allows the brain to resist the development of dementia.
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AsymAD brains show larger nuclei and cellular sizes than age-matched healthy controls.
“even show larger nuclei and cellular sizes than age-matched healthy controls [79].”
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 [79]
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“Specifically, studies have demonstrated that AsymAD brains exhibit no signs of notorious synaptic or neuronal deterioration [8, 42, 73] and, intriguingly, even show larger nuclei and cellular sizes than age-matched healthy controls [79].”
BackgroundSelf-citation
- Authors
- Riudavets, M. A., Iacono, D., Resnick, S. M., O’Brien, R., Zonderman, A. B., Martin, L. J., Rudow, G., Pletnikova, O., & Troncoso, J. C.
- Affiliations
- Johns Hopkins University (US)
- National Institute on Aging (US)
- Corresponding author
- Troncoso, Juan C.
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 28
- Issue
- 10
- Pages
- 1484-1492
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC2694127
- OpenAlex
- W2079058264
- Cited by
- 106
- References
- 15
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 6 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 2 · 2016: 5 · 2015: 8 · 2014: 12 · 2013: 9 · 2012: 5
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Burroughs Wellcome Fund
- National Institutes of Health
- National Institute on Aging (AG 16282, R01AG016282, Z01AG000191, P50AG005146, AG 05146)
- National Institute of Neurological Disorders and Stroke (R01NS052098, NS52098)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, asymptomatic Alzheimer's disease, nuclear hypertrophy, neuronal volume, anterior cingulate cortex, hippocampal CA1, mild cognitive impairment, amyloid-beta, tau protein, stereology, neuronal atrophy
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cell Nucleus, Cognition Disorders, Dementia, Gyrus Cinguli, Hippocampus, Humans, Hypertrophy, Immunity, Innate, Male, Middle Aged, Neurons, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression, Cell Nucleus Size
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