Hypothesis: Modulation of microglial phenotype in Alzheimer's disease drives neurodegeneration
- Resource Type
- Authors
- Andrew G. Murchison
- Source
- Alzheimer's & Dementia. 18:1537-1544
- Subject
- Amyloid
Epidemiology
tau Proteins
Disease
Biology
Blood–brain barrier
Cellular and Molecular Neuroscience
Developmental Neuroscience
Alzheimer Disease
medicine
Humans
Amyloid beta-Peptides
Microglia
Health Policy
Neurodegeneration
Glutamate receptor
medicine.disease
Phenotype
Biochemistry of Alzheimer's disease
Psychiatry and Mental health
medicine.anatomical_structure
Neurology (clinical)
Geriatrics and Gerontology
Neuroscience
- Language
- ISSN
- 1552-5279
1552-5260
The pathophysiology of Alzheimer's disease (AD) remains to be elucidated. The amyloid hypothesis holds explanatory power but has limitations. This article suggests that amyloid deposition and increased permeability of the blood-brain barrier are independent early events in the disease process, which together fashion a distinct microglial activation phenotype. Downstream events including, phagocytosis of synapses and persistent glutamate signaling through N-methyl-D-aspartate receptors drive neurodegeneration and tau pathology. This hypothesis draws on several strands of evidence and aims to illuminate several of the unexplained temporal and spatial features of AD.