Calcium and Neuronal Injury in Alzheimer's Disease: Contributions of β‐Amyloid Precursor Protein Mismetabolism, Free Radicals, and Metabolic Compromisea

MATTSON, MARK P.

doi:10.1111/j.1749-6632.1994.tb44401.x

Cited by 166Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchMedicinal Plants and Neuroprotection

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Calcium and Neuronal Injury in Alzheimer's Disease: Contributions of β‐Amyloid Precursor Protein Mismetabolism, Free Radicals, and Metabolic Compromisea

MATTSON, MARK P.·1994·Annals of the New York Academy of Sciences

DOI 10.1111/j.1749-6632.1994.tb44401.x

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Abstract

Alzheimer's disease (AD) is defined by degeneration of specific populations of neurons and the presence of insoluble aggregates of cytoskeletal proteins and amyloid beta-peptide (A beta) within affected brain regions. Alzheimer's disease does not appear to result from a single alteration, but in some cases of inherited AD a specific genetic defect can precipitate the disease. In this article, metabolic compromise, altered metabolism of the beta-amyloid precursor protein (beta APP), and an excitotoxic form of neuronal injury are considered central to the pathogenesis AD. The hypothesis is forwarded that destabilization of neuronal Ca2+ homeostasis underlies neuronal degeneration and that multiple age-associated and/or genetic alterations contribute to the loss of Ca2+ homeostasis. Recent studies showed that the secreted forms of beta APP (APPss) stabilize intracellular free calcium levels ([Ca2+]i) and protect neurons against excitotoxic insults. In contrast, A beta which arises from alternative processing of beta APP forms free radical peptides and aggregates that destabilize [Ca2+]i and make neurons vulnerable to metabolic insults. Increased expression (eg, Down's syndrome) or altered processing (eg, beta APP mutations) of beta APP may increase the A beta/APPs ratio. The death of neurons in AD most likely has an excitotoxic component because: the vulnerable neurons possess high levels of glutamate receptors; experimentally induced excitotoxicity shows several features simila…

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Several degradation products of cellular activity, such as β-amyloid oligomers and amyloid depositions, have adverse effects on synaptic transmission and cytosolic Ca2+ concentrations and can trigger irreversible neuronal injury.
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Self-citation

Authors: MATTSON, M. P.
Affiliations: University of Kentucky (US)
Corresponding author: MATTSON, MARK P.
ORCID: MATTSON, MARK P.
Venue: Annals of the New York Academy of Sciences
Publisher: Wiley
Published: 1994-12
Volume: 747
Issue: 1
Pages: 50-76
ISSN: 0077-8923 (ISSN-L)
1749-6632
DOI: 10.1111/j.1749-6632.1994.tb44401.x
OpenAlex: W4323874225
Cited by: 166
References: 17
Citations by year: 2026: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 9 · 2012: 7
FWCI: 3.34
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 4399 d)
Locations: Annals of the New York Academy of Sciences (publishedVersion)
PubMed (publishedVersion)
PubMed
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
Keywords: calcium, neuronal injury, Alzheimer's disease, calcium homeostasis, neurodegeneration
MeSH terms: Aging, Alzheimer Disease, Calcium, Free Radicals, Homeostasis, Humans, Nerve Degeneration, Neuronal Plasticity, Neurons, Protein Processing, Post-Translational, Amyloid beta-Protein Precursor, Neurotransmitter Agents, Excitatory Amino Acids

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Calcium and Neuronal Injury in Alzheimer's Disease: Contributions of β‐Amyloid Precursor Protein Mismetabolism, Free Radicals, and Metabolic Compromisea

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