Thanks, Horst, for your insightful comment.

I have to disagree with the "8-9 mainstream hypotheses". The current status is that the debate over the primary cause of Alzheimer's disease (AD) centers on two main hypotheses: the amyloid hypothesis and the vascular hypothesis. The former has been dominant for decades, but increasing evidence supports the latter, recognizing that cerebrovascular dysfunction, including reduced cerebral blood flow and blood-brain barrier disruption, plays a crucial role in AD pathogenesis. The evidence from epidemiological, neuroimaging, pathological, and clinical studies is too compellingly linking chronic brain hypoperfusion to AD risk factors and preclinical manifestations. However, some researchers argue for a convergence of both hypotheses, suggesting that vascular pathology and amyloid accumulation may act synergistically in AD progression. That's why I'm calling it a vicious cycle of both, that you can enter from either point. But considering the AD pathogenesis while excluding the vascular hypothesis doesn't make sense with our current evidence.