Ekaterina Rogaeva, PhD, Assistant Professor, Department of Medicine, University of Toronto, Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON.
To date, four genes responsible for Alzheimer disease (AD) have been identified. However, in about 50% of the familial AD cases, there is no known cause of the disease. The majority of AD cases are sporadic with onset after 65 years of age. The apolipoprotein E gene is the only well-replicated risk factor for late-onset AD. Up to 5% of AD cases are early-onset AD, for which genetic analyses have found three causal genes: b-amyloid precursor protein, presenilin-1 and presenilin-2. Treatment and diagnostic strategies based on genetic knowledge are now about to reach the clinic.
Key words: Alzheimer disease, presenilin, gene, bAPP, apolipoprotein E.
Alzheimer disease (AD) is a progressive dementia and is the fourth leading cause of death in industrialized countries. AD brain pathology is characterized by neuronal loss, intra-neuronal tau-accumulation and extracellular amyloid plaques. The plaques consist mainly of Ab40/42 peptides generated by cleavage of the b-amyloid precursor protein (bAPP) (Figure 1). The longer and more neurotoxic isoforms, Ab42, appear to be elevated in the brains of individuals affected with either sporadic or familial AD, implying that they have a shared pathogenetic mechanism.