Vulnerability of Select Neuronal Types to Alzheimer's Disease
Abstract
From a morphological perspective, Alzheimer's disease (AD) is primarily a degenerative disorder of the neuronal cytoskeleton involving lipofuscin-laden cortical projection neurons with long, thin, and sparsely myelinated axons. The neocortical primary fields, relatively small in extent but functionally sophisticated, exhibit an early and brief myelination cycle, whereas the much more expansive but relatively simply organized association areas undergo a late and prolonged myelination process. The greater the degree of myelination and the less intense the pigmentation, the more resistant a given projection neuron may be to oxidative stress as well as to the development of AD-related neurofibrillary changes and vice versa. The neurofibrillary pathology commences from those cortical areas that are less completely myelinated and gradually progresses to the most functionally developed cortical fields that display the highest degree of myelination, thereby reflecting a hierarchy in the susceptibility of diverse cortical areas to the evolution of the AD-associated cytoskeletal pathology.
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Lipofuscin is a pathological autofluorescent lipopigment that relates to neuronal aging and vulnerability in AD brain.
“a pathological autofluorescent lipopigment of obscure origin since its discovery in 1840 (reviewed in ref.43) that relates to neuronal aging35,43 and vulnerability in AD brain44”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [44]
When ApoE carries PUFA-CE, LDLR-dependent internalization caused lysosomal deposition of lipofuscin.
“Specifically, when ApoE carries PUFA-CE, LDLR-dependent internalization caused lysosomal deposition of lipofuscin, a pathological autofluorescent lipopigment of obscure origin since its discovery in 1840 (reviewed in ref.43) that relates to neuronal aging35,43 and vulnerability in AD brain44.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [44]
Long and poorly myelinated cortical neurons with higher lipofuscin burden in the transentorhinal cortex are the most vulnerable to neurofibrillary tangle formation, and lipofuscin-free neurons are generally more resilient in AD.
“long and poorly myelinated cortical neurons with higher lipofuscin burden in the transentorhinal cortex are the most vulnerable to neurofibrillary tangle formation, and lipofuscin-free neurons are generally more resilient in AD44.”
From Decreased lipidated ApoE‐receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes (2025) · cites this paper as [44]
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- Authors
- BRAAK, H., DEL TREDICI, K., SCHULTZ, C., & BRAAK, E.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- BRAAK, HEIKO
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2000-12
- Volume
- 924
- Issue
- 1
- Pages
- 53-61
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- OpenAlex
- W1991500873
- Cited by
- 150
- References
- 1
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 7 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 8 · 2014: 6 · 2013: 10 · 2012: 8
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- 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, neuronal vulnerability, cortical projection neurons, myelination, lipofuscin, oxidative stress, neurofibrillary tangles, association cortex
- MeSH terms
- Alzheimer Disease, Animals, Biological Evolution, Humans, Myelin Sheath, Neurons, Primates, Oxidative Stress
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