Corewell Health: The new name for Beaumont. Here to make health better.

Molecular mechanisms of AD pathogenesis

Pathological manifestation of Alzheimer’s disease (AD) precedes more than a decade before the appearance of clinical symptoms (e.g., cognitive impairment). During this pre-clinical phase both intra and extra-neuronal pathologies including β-amyloid (Aβ) plaques, neurofibrillary tangles, dystrophic neurites (DNs) formation, mitochondrial degeneration, and glial dysfunction advance AD progression to the clinical phase (Fig. 1). Currently, there is no effective drug to prevent or cure AD. Large number of clinical trials fails and the complexity of disease mechanism suggest that AD diagnosis and disease modifying strategies need to be targeted at early pre-clinical stage. Hence, identifying early diagnosis biomarkers and understanding the cellular/molecular mechanism of etiopathphysiology are prerequisite for effective AD drug development.


The cellular homeostasis relies on spontaneous degradation of its undesired components through autophagy and endo-lysosomal pathways; both processes ultimately are targeted to the lysosomes. Increasing evidence suggests that autophagy-lysosomal dysfunctions contribute to the initiation and progression of AD by disrupting the degradation of toxic molecules such as Aβ and tau. We reported that accumulation of dysfunctional lysosomes and ER-mitochondria inclusion in Aβ core surrounding DNs occur during Aβ plaque initiation in AD brains. Although, Aβ deposition commonly found in non-demented elderly brain, the accumulation of cellular organelles and proteins in DN is a distinguishing feature in AD brains.


Our long-term research goal is to determine novel pathways that are associated with neuronal/glial homeostatic susceptibility in AD and to target DN forming organelles/proteins (Fig. 1) for developing early AD diagnostic biomarkers by focusing on specific areas of research. 

Alzheimer's research

Fig 1. We focus on the AD pathogenic mechanism to develop early diagnostic biomarkers and identify therapeutic treatments by focusing on cellular homoeostatic defect that initiate/elevate Aβ deposition, and DNs forming proteins and organelles.

Areas of Research

Additional Resources