Associations between regional blood-brain barrier permeability, aging, and Alzheimer's disease biomarkers in cognitively normal older adults.
Level 4 - case-series / case-control
Cross-sectional observational imaging study
PubMed 38837947 · doi:10.1371/journal.pone.0299764
What was done
Dynamic contrast-enhanced MRI (DCE-MRI) measured blood-brain barrier permeability (quantified by Ktrans across 37 cortical regions) in 31 cognitively normal older adults and 10 young adults from the Berkeley Aging Cohort Study. Older adults also underwent PiB-PET for amyloid-beta and flortaucipir-PET for tau. Permeability differences between age groups, as well as associations with APOE4 carrier status, sex, and PET biomarkers within age-vulnerable composite regions, were evaluated using repeated measures ANOVA, linear models, and sparse canonical correlation analysis.
What was found
Older adults showed greater blood-brain barrier permeability than young adults predominantly in the temporal lobe, along with parietal, occipital, and frontal regions (no specific numerical values or effect sizes provided in the abstract). Among older adults, APOE4 carriers had significantly higher permeability in age-affected regions, whereas sex and binary amyloid-beta positivity showed no differences. While overall composite permeability was not directly linked to global amyloid-beta, sparse canonical correlation analysis linked increased regional permeability to increased amyloid deposition in temporal and parietal regions. Permeability was not significantly associated with tau burden, though a trend for an amyloid-beta by tau interaction was noted.
Why it matters
The findings suggest that normal aging involves regional microvascular barrier breakdown that overlaps anatomically with early Alzheimer's disease pathology and is exacerbated by the APOE4 genotype.
Limits
The sample size is very small (31 older adults, 10 young adults), limiting statistical power. The cross-sectional design cannot establish whether barrier leakage precedes, causes, or results from amyloid pathology. The abstract lacks quantitative effect sizes, confidence intervals, and exact p-values.
Cited by
- supports The blood-brain barrier naturally becomes less functional and increasingly permeable as humans age.