Fig. 6

The systemic aetiology hypothesis of AD. Central and peripheral factors synergistically contribute to the development of AD. Central factors initiate Aβ overproduction or insufficient clearance, cause Aβ accumulation and downstream pathologies, eventually lead to neurodegeneration and dementia. Aβ aggregates together with peripheral factors exert damage to BBB. BBB dysfunction leads to neurodegeneration and dementia in both Aβ-dependent and -independent pathways. AD, Alzheimer’s disease; BBB, blood-brain barrier; VRF, vascular risk factor