There is an ongoing debate surrounding the mechanisms of Alzheimer’s disease, with most of the focus on protein aggregation, specifically amyloid-β and tau. However, alternative theories have emerged in recent years, leading to research programs exploring inflammatory signaling and other potential mechanisms. This paper challenges the conventional thinking by shifting attention away from protein aggregates and towards other aspects of brain biology in aging individuals.
Despite extensive research on amyloid and tau proteins, current treatments for Alzheimer’s disease have been unsuccessful. This prompts a reevaluation of the classic hypotheses and the need for a new perspective. The fixation on amyloid and tau may be limiting the exploration of other genes and proteins involved in AD pathology. The review suggests that impaired neurogenesis could be a crucial factor in the early stages of AD, preceding amyloid and tau accumulation. By delving into the molecular mechanisms of compromised neurogenesis, a deeper understanding of AD pathogenesis can be achieved.
The proposed hypothesis highlights the roles of Notch signaling and heparan sulfate proteoglycans in impaired neurogenesis. While recognizing the importance of amyloid and tau, it advocates for further investigation beyond these theories. The review proposes studying altered heparan sulfate sulfation patterns as potential initiators of AD. By challenging traditional views on AD triggers and suggesting new avenues of exploration, this review offers a fresh perspective on the disease.
