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Updated: Nov 10, 2025
Detecting Amyloid-β Accumulation via Immunofluorescent Staining in a Mouse Model of Alzheimer's Disease
Published on: April 19, 2021
Age, sex, and cerebral microbleeds in EFAD Alzheimer disease mice
Mafalda Cacciottolo1, Todd E Morgan1, Caleb E Finch2
1Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Abstract:
Cerebral microbleeds (MBs) increase at later ages in association with increased cognitive decline and Alzheimer Disease (AD). MB prevalence is also increased by APOE4 and hypertension. In EFAD mice (5XFAD+/-/human APOE+/+), cerebral cortex MBs are most prevalent in E4 females at 6 months, paralleling plaque amyloid. We evaluated MBs at 2, 4, and 6 months in relation to amyloid in plaques and cerebral amyloid angiopathy (CAA) by age, sex, APOE allele, and blood pressure. At 2 mo, MBs were 50% more numerous than plaques, followed by decreased ratio of MBs:Aβ plaques with female excess to 6 mo. The stable size of MBs suggests MBs arise as single events of extravasation, which may "seed" plaque formation. Blood pressure was normal from 2 to 6 months, minimizing a role of hypertension. Memory, assessed by fear conditioning, decreased with age in correlation with MBs and amyloid. Cortical layer analysis showed prevalent MBs and plaque in layers 4 and 5. Contrarily, CAA was prevalent in layers 1 and 2, discounting its contribution to MBs.
Insights
Cerebral microbleeds (MBs) and amyloid plaques are linked to cognitive decline in Alzheimer
Area of Science:
- Neuroscience
- Neuropathology
- Genetics
Background:
- Cerebral microbleeds (MBs) and amyloid plaques are associated with cognitive decline and Alzheimer Disease (AD).
- APOE4 genotype and hypertension are known risk factors for increased MB prevalence.
- EFAD mice models offer insights into AD pathogenesis.
Purpose of the Study:
- To investigate the relationship between MBs, amyloid plaques, and cerebral amyloid angiopathy (CAA) in EFAD mice.
- To evaluate the influence of age, sex, APOE allele, and blood pressure on MBs and amyloid pathology.
- To explore the potential role of MBs in seeding plaque formation and their correlation with cognitive function.
Main Methods:
- Utilized EFAD mice (5XFAD+/-/human APOE+/+) at 2, 4, and 6 months of age.
- Quantified MBs, amyloid plaques, and CAA in the cerebral cortex.
- Assessed memory function using fear conditioning.
- Monitored blood pressure throughout the study.
Main Results:
- MBs were more numerous than amyloid plaques early on, with a decreasing ratio over time and a female predominance.
- Stable MB size suggests extravasation events may initiate plaque formation.
- Cognitive decline correlated with increased MBs and amyloid burden.
- MBs and plaques were concentrated in cortical layers 4 and 5, while CAA was in layers 1 and 2.
Conclusions:
- MBs and amyloid pathology are closely linked in EFAD mice, contributing to cognitive decline.
- The findings suggest MBs might precede and seed amyloid plaque formation.
- Hypertension was not a significant factor in this model, but age and sex influenced pathology distribution.
