Mutations in the PSEN1 and PSEN2 genes are linked to early-onset familial Alzheimer's Disease (FAD). These mutations result in altered γ-secretase activity, leading to an increased ratio of amyloid-β42 to amyloid-β40. Amyloid-β42 is more prone to aggregation and is a principal component of the amyloid plaques found in the brains of Alzheimer's patients. Histological examinations of brain tissues from affected individuals typically reveal these plaques along with neurofibrillary tangles composed of hyperphosphorylated tau protein.
