Abstract:

Alzheimer’s disease (AD) is the most common form of dementia representing a major problem for public health. In 2017 there were an estimated 50 million patients worldwide and this number is expected to almost double every 20 years, reaching 75 million in 2030 and 131.5 million in 2050 (https://www.alz.co.uk/research/statistics). Clinically there are two forms of the disease: the sporadic form (also called late onset AD, LOAD) and the familial form (FAD).LOAD is the most common form. Its prevalence increases with advancing age from 1% in the 65–70 years old cohort to more that 30% after the age of 85. It is characterized by moderate to extreme severity with the advancing age being the main risk factor for LOAD. Familiar AD represents some 5–10% of all AD cases. FAD is linked to mutations in a specific set of genes, most often in the genes encoding amyloid precursor protein (APP) and the presenilins (PS) 1 and 2. Interestingly, the vast majority of AD related mutations are located on PS1 thus identifying this protein as one of the main targets for FAD-modifying therapies. Here we address the role of AD-related presenilin mutations for Ca²⁺ dyshomeostasis and in vivo neural network dysfunction in AD.