Alzheimer's disease and related dementias: prospects for treatment

Alzheimer's disease (AD) represents a major challenge to healthcare costs and to academic and pharmaceutical research efforts. The approval in 1996 of the first of the second generation acetylcholinesterase inhibitors, donepexil (Aricept, Eisai/Pfizer), has offered new hope, albeit palliative, to AD sufferers and care givers. Research has continued on the genetics of AD with the identification of the autosomal dominant inheritance of genetic defects in one of three distinct genes coding for the presensilins 1 and 2 and amyloid precursor protein (APP). While driving an ever increasing research effort related to the production, deposition and clearance of Abeta peptides, these mutations account for less than 10% of the AD cases reported, indicating that other causative factors, both genetic and environmental, may contribute to the pathophysiology of AD unrelated to familial cohorts. A newly developed transgenic mouse model and a broader appreciation of the multifactorial nature of this complex, chronic disease state may help provide a more objective approach to understanding the disease per se as opposed to amyloid neurotoxicity specifically which may or may not be causative.