Piecing together the Alzheimer’s puzzle: Lecanemab’s role in treatment
Sporadic Alzheimer’s disease (SAD) has a complex etiology that includes genetic, metabolic, environmental, viral and other factors whereas familial Alzheimer’s disease (FAD) is primarily linked to genetic mutations in the APP and presenilin genes, PSEN1 and PSEN2 [3]. APOE is a polymorphic protein with three isoforms: APOE2, APOE3 and APOE4, where APOE4 is the strongest genetic risk factor for SAD [4].
Exploring Alzheimer’s: an unclear pathogenesis
Amyloid pathogenesis begins with altered cleavage of APP, an integral protein on the plasma membrane, by BACE1 and γ-secretases to produce insoluble Aβ monomers, Aβ then oligomerizes, diffuses into synaptic clefts and interferes with synaptic signaling [5,6]. Extracellular beta–amyloid deposits (seen in senile plaques) and intracellular NFTs (neurofibrillary tangles) are the two pathologic hallmarks of Alzheimer’s disease [7,8].
