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Cited by 359Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Synaptic basis of Alzheimer’s disease: Focus on synaptic amyloid beta, P-tau and mitochondria

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John, Albin, Reddy, P. Hemachandra·2021·Ageing Research Reviews
DOI 10.1016/j.arr.2020.101208PMC PMC7770124
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Abstract

Alzheimer's disease (AD) is a progressive and synaptic failure disease. Despite the many years of research, AD still harbors many secrets. As more of the world's population grows older, researchers are striving to find greater information on disease progression and pathogenesis. Identifying and treating the markers of this disease, or better yet, preventing it all together, are the hopes of those investing in this field of study. Several years of research revealed that synaptic pathology and mitochondrial oxidative damage are early events in disease progression. Loss of synapses and synaptic damage are the best correlates of cognitive deficits found in AD patients. As the disease progresses, there are significant changes at the synapse. These changes can both shed greater light onto the progression of the disease and serve as markers and therapeutic targets. This article addresses the mechanisms of synaptic action, mitochondrial regulation/dysregulation, resulting synaptic changes caused by amyloid beta and phosphorylated tau in AD progression. This article also highlights recent developments of risk factors, genetics and ApoE4 involvement, factors related to synaptic damage and loss, mislocalization of amyloid beta and phosphorylated tau, mitophagy, microglial activation and synapse-based therapies in AD. Furthermore, impairments in LTD and reactivation of microglia are discussed.

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  • The PRKCA gene encodes protein kinase Cα (PKCα), which participates in synaptic loss resulting from the accumulation of amyloid-β in AD neuropathology.

    “The PRKCA gene encodes protein kinase Cα (PKCα), which participates in synaptic loss resulting from the accumulation of amyloid-β (Aβ) in AD neuropathology [73, 74].”

    From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [74]

    The “Amyloid Beta and Alzheimer’s Disease” section states that Aβ accumulation induces synaptic damage in AD neurons, supporting that part of the claim. The passages found for PRKCA, PKCα, and protein kinase C do not identify PRKCA as encoding PKCα or link PKCα to that damage, so the protein-specific attribution is unsupported by our copy. Page numbers were not available. (LLM, conf=0.86)

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Authors
John, A., & Reddy, P. H.
Affiliations
Texas Tech University (US)
Corresponding author
Reddy, P. Hemachandra
ORCID
Venue
Ageing Research Reviews
Publisher
Elsevier BV
Published
2021-01
Volume
65
Pages
101208
ISSN
1568-1637 (ISSN-L)
DOI
10.1016/j.arr.2020.101208
PMC
PMC7770124
OpenAlex
W3097560931
Cited by
359
References
78
Citations by year
2026: 50 · 2025: 71 · 2024: 77 · 2023: 67 · 2022: 65 · 2021: 29
FWCI
5.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Ageing Research Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (AG042178, AG069333, AG066347, AG047812, AG060767, NS105473)
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, synaptic dysfunction, amyloid-beta, phosphorylated tau, mitochondrial dysfunction, oxidative stress, synaptic loss, APOE ε4, mitophagy, microglial activation, long-term depression, disease progression, risk factors
MeSH terms
Reelin Protein, Alzheimer Disease, Humans, Mitochondria, Synapses, Amyloid beta-Peptides, tau Proteins, Apolipoprotein E4

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