Alzheimer's disease, a multifactorial disorder seeking multitherapies

Abstract 

Alzheimer's disease (AD) is multifactorial and apparently involves several different etiopathogenic mechanisms. There are at least five subgroups of AD based on cerebrospinal fluid levels of Aβ_1–42, a marker of beta-amyloid (Aβ) plaques, and tau and ubiquitin, two markers of neurofibrillary tangles. These different AD subgroups may respond differently to a given disease-modifying drug, and hence, different therapeutic drugs for different disease subgroups might be required. Stratification of AD patients by disease subgroups in clinical trials is critical to the successful development of potent disease-modifying drugs. Levels of disease markers in the cerebrospinal fluid are promising, both in identifying various subgroups of AD and in monitoring the response to therapeutic drugs.

Keywords: Alzheimer disease subgroups, Cerebrospinal fluid, CSF biomarkers, Aβ_1–42, Tau, Ubiquitin, Alzheimer disease therapeutics, Neurofibrillary degeneration, β-amyloid