Pathological changes in frontal cortex from biopsy to autopsy in Alzheimer's disease
Abstract
We evaluated the change in density of total senile plaques, plaque subtypes, and neurofibrillary tangles, from biopsy to autopsy in left frontal cortical sections from four patients with clinically typical Alzheimer's disease (AD). Comparisons were made on sections stained with modified Bielschowsky and Thioflavin S. In two cases, comparisons were also made on tissue stained with a monoclonal Alz-50 antibody and an antiserum to A beta (beta-amyloid protein). Despite a marked decline in mental status over several years of follow-up clinical evaluations, there was no consistent significant change in numerical density of plaques or tangles among the four cases. However, we did find fewer primitive plaques in the autopsy specimens. These results from longitudinally evaluated persons with typical AD suggest that although plaques and tangles may serve as adequate markers of the presence of AD, their numerical density within a single neocortical region may not reflect dementia severity. This conclusion supports the results of recent cross-sectional studies on the progression of pathology among persons with AD.
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Aβ42, due to its hydrophobicity, more readily forms toxic oligomers and amyloid plaques, which are central to the amyloid cascade hypothesis of Alzheimer's disease pathogenesis.
“Aβ42, due to its hydrophobicity, more readily forms toxic oligomers and amyloid plaques, which are central to the amyloid cascade hypothesis of AD pathogenesis [20, 21].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [20]
Tau pathology is linked to cognitive decline, may progress more rapidly than Aβ accumulation, and correlates with neuroinflammation, making it a valuable prognostic marker.
“Numerous studies have linked tau pathology to cognitive decline, with some evidence suggesting it progresses more rapidly than Aβ accumulation and correlates with neuroinflammation, making it a valuable prognostic marker [20, 25–28].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [20]
Lesion turnover (i.e. AβPs being possibly reabsorbed during life so that they would not be 'counted' at autopsy) seems to occur in some subjects.
“Often neglected is the question of lesion turnover (i.e. AβPs being possibly reabsorbed during life so that they would not be “counted” at autopsy), which seems to occur in some subjects (70, 270).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [270]
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- Authors
- Bennett, D. A., Cochran, E. J., Saper, C. B., Leverenz, J. B., Gilley, D. W., & Wilson, R. S.
- Affiliations
- Rush University Medical Center (US)
- University of Washington (US)
- Corresponding author
- Bennett, David A.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 1993-11
- Volume
- 14
- Issue
- 6
- Pages
- 589-596
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2083758861
- Cited by
- 67
- References
- 66
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 1 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 10161, AG09466, P30AG010161, P01AG009466)
- 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, frontal cortex, amyloid plaques, neurofibrillary tangles, plaque density, dementia severity, longitudinal follow-up, amyloid-beta, thioflavin S staining, disease progression
- MeSH terms
- Alzheimer Disease, Antibodies, Monoclonal, Antigens, Bethanechol Compounds, Cerebral Cortex, Cognition, Humans, Injections, Intraventricular, Amyloid beta-Peptides, Neurofibrillary Tangles
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