Cognitive impact of neuronal pathology in the entorhinal cortex and CA1 field in Alzheimer's disease
Abstract
The relative contribution of Alzheimer's disease (AD) hippocampal neuronal pathology in cognitive decline is still a matter of debate. To address this issue, we performed a stereological analysis of layer II of the entorhinal cortex and the CA1 field of the hippocampus in 34 autopsy cases covering the whole spectrum of old age and Clinical Dementia Rating (CDR) scores. In both areas, the proportion of neurofibrillary tangle (NFT)-containing neurons increased steadily as a function of the CDR score. Questionable dementia was associated with a 1.9% neuronal loss in the entorhinal cortex and 26% in the CA1 field. NFT numbers predicted only 38% of the neuron number variability in the entorhinal cortex and 55% in the CA1 field. Neuron counts in the entorhinal cortex and both neuron and NFT counts in the CA1 field were significantly associated with cognitive status explaining 25% and 44% of the CDR variability, respectively. Our data reveal a dissociation between the patterns of progression of NFT and neuronal loss in the entorhinal cortex and CA1 field. Moreover, they show that less than 50% of the cognitive variability may be attributable to AD neuronal pathology in these areas.
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Several studies have reported a strong negative correlation between neuronal counts and NFT number in the CA1 subfield, suggesting that the progression of brain atrophy and the progression of NFT are strongly associated.
“Moreover, several studies have reported a strong negative correlation between neuronal counts and NFT number in the CA1 subfield (Fukutani et al., 2000; Von Gunten et al., 2006) suggesting that the progression of brain atrophy and the progression of NFT are strongly associated (Whitwell et al., 2008).”
From Hippocampal subfield volumetry in mild cognitive impairment, Alzheimer's disease and semantic dementia (2013) · cites this paper as Von Gunten et al., 2006
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- Authors
- GUNTEN, A., KOVARI, E., BUSSIERE, T., RIVARA, C., GOLD, G., BOURAS, C., HOF, P., & GIANNAKOPOULOS, P.
- Affiliations
- University of Lausanne (CH)
- Icahn School of Medicine at Mount Sinai (US)
- University of Geneva (CH)
- Corresponding author
- HOF, P
- GIANNAKOPOULOS, P
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 27
- Issue
- 2
- Pages
- 270-277
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2085182512
- Cited by
- 101
- References
- 39
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 6 · 2012: 3
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG-02219, AG 05138, P50AG005138, P01AG002219)
- 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 › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Alzheimer's disease, entorhinal cortex, CA1 field, hippocampus, neurofibrillary tangles, neuronal loss, cognitive decline, Clinical Dementia Rating, stereology, neuronal pathology, dementia progression
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Brain Mapping, Cell Count, Cognition Disorders, Diagnosis, Computer-Assisted, Female, Hippocampus, Humans, Immunohistochemistry, Male, Middle Aged, Neurons, Neurofibrillary Tangles, Entorhinal Cortex
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