Current therapeutic targets for the treatment of Alzheimer’s disease

Abstract

Alzheimer’s disease is a progressive neurodegenerative disease for which no cure exists. There is a substantial need for new therapies that offer improved symptomatic benefit and disease-slowing capabilities. In recent decades there has been substantial progress in understanding the molecular and cellular changes associated with Alzheimer’s disease pathology. This has resulted in identification of a large number of new drug targets. These targets include, but are not limited to, therapies that aim to prevent production of or remove the amyloid-β protein that accumulates in neuritic plaques; to prevent the hyperphosphorylation and aggregation into paired helical filaments of the microtubule-associated protein tau; and to keep neurons alive and functioning normally in the face of these pathologic challenges. We provide a review of these targets for drug development.

Keywords::

• amyloid-β
• β-secretase
• γ-secretase
• Alzheimer’s disease
• dementia
• immunotherapy
• tau
• therapeutic
• treatment

Financial & competing interests disclosure

Joshua Grill has been site investigator for clinical trials sponsored by Elan, Janssen, Bristol-Myers Squibb, Medivation, Pfizer and the Alzheimer’s Disease Cooperative Study (ADCS). Jeffrey Cummings has acted as a consultant for Abbott, Acadia, Accera, Adamas, Astellas, Avanir, Bristol-Myers Squibb, CoMentis, Eisai, Elan, EnVivo, Forest, GlaxoSmithKline, Janssen, Lilly, Lundbeck, Medivation, Merck, Merz, Myriad, Neuren, Novartis, Noven, Pfizer, Prana, reMYND, Schering-Plough, Sonexa, Takeda, Toyama and Wyeth. He also has stock in Adamas, Prana and Sonexa; is on the Speakers’ Bureau for Eisai, Forest, Janssen, Lundbeck, Merz, Novartis and Pfizer; and owns copyright of the Neuropsychiatric Inventory. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Notes

^†Targets for which US FDA-approved medications exist.

Aβ: Amyloid-β.