The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer's disease.
Abstract
OBJECTIVE: To determine the spatiotemporal mapping of neurofibrillary degeneration (NFD) in normal aging and the different stages of AD. BACKGROUND: The pathophysiologic significance of AD lesions, namely amyloid plaques and neurofibrillary tangles, is still unclear, especially their interrelationship and their link with cognitive impairment. METHODS: The study included 130 patients of various ages and different cognitive statuses, from nondemented control subjects (n = 60, prospective study) to patients with severe definite AD. Paired helical filaments (PHF)-tau and Abeta were used as biochemical and histologic markers of NFD and amyloid plaques, respectively. RESULTS: NFD with PHF-tau was systematically present in variable amounts in the hippocampal region of nondemented patients age >75 years. When NFD was found in other brain areas, it was always along a stereotyped, sequential, hierarchical pathway. The progression was categorized into 10 stages according to the brain regions affected: transentorhinal cortex (S1), entorhinal (S2), hippocampus (S3), anterior temporal cortex (S4), inferior temporal cortex (S5), medium temporal cortex (S6), polymodal association areas (prefrontal, parietal inferior, temporal superior) (S7), unimodal areas (S8), primary motor (S9a) or sensory (S9b, S9c) areas, and all neocortical areas (S10). Up to stage 6, the disease could be asymptomatic. In all cases studied here, stage 7 individuals with two polymodal association areas affected by tau pathologic states were cognitively impaired. CONCLUSIONS: The relationship between NFD and Alzheimer-type dementia, and the criteria for a biochemical diagnosis of AD, are documented, and an association between AD and the extent of NFD in defined brain areas is shown.
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Braak and Braak reported at autopsy that NFT distribution begins in entorhinal cortices, then spreads to higher-order temporoparietal association cortices, then frontal areas, and finally primary sensory and visual areas.
“Braak and Braak (1997) noted at autopsy that NFT distribution was initially restricted to entorhinal cortices, spreading to higher-order temporoparietal association cortices, then to frontal, and ultimately, to primary sensory and visual areas (Delacourte et al., 1999;Price and Morris, 1999).”
From Dynamics of Gray Matter Loss in Alzheimer's Disease (2003) · cites this paper as Delacourte et al., 1999
The hippocampus and adjacent areas are deteriorated first and foremost in Alzheimer's disease.
“Since this structure and adjacent areas are deteriorated first and foremost in Alzheimer's disease [4,19,36], differentiating the mesial temporal GM evolution in normal and pathological aging constitutes a key issue.”
From Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging (2009) · cites this paper as [19]
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- Authors
- Delacourte, A., David, J. P., Sergeant, N., Buée, L., Wattez, A., Vermersch, P., Ghozali, F., Fallet-Bianco, C., Pasquier, F., Lebert, F., Petit, H., & Di Menza, C.
- Affiliations
- Inserm (FR)
- From the Unité INSERM 422 (Drs. DelacourteDavid, Sergeant, Buée, and Vermersch, and A. Wattez), Lille; Gerontology Clinic (Drs. David, Ghozali, Fallet-Bianco, and Di Menza), Emile Roux Hospital, Limeil Brévannes; and Memory Clinic (Drs. Pasquier, Lebert, and Petit), Department of Neurology, CHU&U, Lille, France.
- Venue
- Neurology
- Published
- 1999-04
- Volume
- 52
- Issue
- 6
- Pages
- 1158-1158
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2093488421
- Cited by
- 828
- References
- 41
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 11 · 2023: 25 · 2022: 21 · 2021: 29 · 2020: 26 · 2019: 35 · 2018: 38 · 2017: 31 · 2016: 38 · 2015: 31 · 2014: 31 · 2013: 50 · 2012: 35
- FWCI
- 15.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- 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
- neurofibrillary degeneration, Alzheimer's disease, normal aging, paired helical filaments, tau protein, amyloid plaques, amyloid-beta, hippocampus, entorhinal cortex, disease staging, cognitive impairment
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Brain, Female, Humans, Immunohistochemistry, Male, Blotting, Western, Neurofibrillary Tangles
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