Molecular pathology of Alzheimer's disease

Abstract

The abnormal appearance of cerebral β-amyloid peptide (Aβ) and neurofibrillary tangles are the major pathological characteristics of Alzheimer's disease (AD). The disease in some early onset cases develops due to mutations in the gene coding for the β-amyloid precursor protein (βAPP), although the majority (> 80%) of early onset familial AD is caused by a gene on chromosome 14. Advances in the understanding of the normal and abnormal processing of βAPP and the association and role of the APOE locus in late onset disease are discussed. The existing theoretical pathogenic models of AD do not satisfactorily encompass these findings and the specific roles of βAPP and Aβ are not clear. Particularly, it is unknown whether, in the general case, these molecules are central to disease causation or are secondarily inculcated by abnormalities in fundamental regulatory processes such as calcium homeostasis or phosphorylation status