Biochemistry and Molecular Biology of Amyloid β‐Protein and the Mechanism of Alzheimer's Disease
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All high-penetrance AD genetic risk alleles (APOE ε4 allele, Down syndrome, APP mutations and duplications, PSEN1 and PSEN2 mutations) have been linked in various experimental systems with increased Aβ deposition and increased formation of putative toxic Aβ peptide species.
“All high-penetrance AD genetic risk alleles (i.e. APOE ε4 allele, Down syndrome, APP mutations and duplications, PSEN1 and PSEN2 mutations) have been linked in various experimental systems with increased Aβ deposition and increased formation of putative toxic Aβ peptide species (46, 55-57).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [46]
Abundant evidence from many independent studies indicates that Aβ peptides and other plaque substances (in their various molecular forms) may be neurotoxic, both directly and through secondary responses to stress, injury, and inflammation.
“Abundant evidence from many independent studies indicates that Aβ peptides and other plaque substances (in their various molecular forms) may be neurotoxic, both directly and through secondary responses to stress, injury, and inflammation (46, 82, 83).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [46]
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Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050 · see citing works
Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease
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Classification and basic pathology of Alzheimer disease
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Interaction between Aβ and Tau in the Pathogenesis of Alzheimer’s Disease
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Matrix metalloproteinases and their multiple roles in neurodegenerative diseases
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Oxidative stress, protein modification and Alzheimer disease
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Glucose Transporters in Brain: In Health and in Alzheimer’s Disease
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“…revised recently to include the notions that smaller soluble A oligomers may play an early and significant role in AD and correlate with the impairment in cognitive function, learning, and memory (Lue et al., 1999; McLean et al., 1999; Lesné et al., 2006, 2008; Cheng et al., 2007; Selkoe, 2008).”
BackgroundWhite, M. R., Kandel, R., Tripathi, S., Condon, D., Qi, L., Taubenberger, J., & Hartshorn, K. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101364 · Cited by 193 · see citing works
Zeineh, M. M., Chen, Y., Kitzler, H. H., Hammond, R., Vogel, H., & Rutt, B. K. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.05.022 · Cited by 151 · see citing works
Genetic architecture of Alzheimer's disease
Neuner, S. M., TCW, J., & Goate, A. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104976 · Cited by 126 · see citing works
“…AD is a neurodegenerative disease defined by the presence of extracellular plaques primarily composed of beta-amyloid (Aβ) protein, a byproduct of sequential cleavage of the amyloid precursor protein (APP) by the enzymatic complexes beta (β) and gamma (γ) secretase (Selkoe, 2008; Hardy, 1997).”
Is synaptic loss a unique hallmark of Alzheimer’s disease?
Scheff, S. W., Neltner, J. H., & Nelson, P. T. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.028 · Cited by 118 · see citing works
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Calcium-Sensing Receptors of Human Neural Cells Play Crucial Roles in Alzheimer's Disease
Chiarini, A., Armato, U., Liu, D., & Dal Prà, I. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00134 · Cited by 51 · see citing works
- Authors
- Selkoe, D. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Dennis J. Selkoe
- ORCID
- Dennis J. Selkoe
- Venue
- Handbook of Clinical Neurology
- Publisher
- Elsevier
- Published
- 2008
- Volume
- 89
- Pages
- 245-260
- ISSN
- 0072-9752 (ISSN-L)
- OpenAlex
- W1575511938
- Cited by
- 137
- References
- 124
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 8 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 11 · 2016: 12 · 2015: 9 · 2014: 10 · 2013: 11 · 2012: 16
- FWCI
- 29.29
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Handbook of clinical 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
- Alzheimer's disease, amyloid-beta, amyloid plaques, neurofibrillary tangles, amyloid fibrils, frontotemporal dementia, microglia, reactive astrocytes, risk assessment, mild cognitive impairment, disease pathobiology
- MeSH terms
- Alzheimer Disease, Biochemistry, Humans, Models, Biological, Molecular Biology, Amyloid beta-Peptides
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