Fig. 2

Model of how early life experiences could modulate later AD vulnerability or resilience. Early life experiences directly modulate AD pathogenic pathways by altering tau phosphorylation and production and clearance of Aβ, resulting in a higher pathological load. Secondly, early life experiences determine establishment of a cognitive and/or brain reserve, yielding the brain more vulnerable to pathological insults. Combined, these two pathways mediate effects of early life experiences on vulnerability or resilience of the brain to AD. Aβ amyloid beta, AD Alzheimer’s disease, APP amyloid precursor protein, Arc activity regulated cytoskeleton-associated protein, BACE1 β-APP cleaving enzyme 1, BBB blood–brain barrier, CORT corticosterone, ELS early life stress, EGR1 early growth response protein 1, HPA hypothalamic–pituitary–adrenal, REST repressor element-1 silencing transcription factor, EH early handling, NFT neurofibrillary tangles