The vasculature in Alzheimer’s disease: a new therapeutic target for an old disease?

Abstract

Alzheimer’s disease (AD) is an age-related disorder characterized by progressive cognitive decline and dementia. AD is an irreversible neurodegenerative disease that affects more than 5.3 million people in the USA and is projected to sharply increase to 8 million by 2030 [101]. Every 69 s, someone in America develops AD, and it is the sixth leading cause of death. In 2011, the cost of caring for those with AD to American society will total an estimated US$183 billion. Unless something is done, the costs of AD in 2050 will total $1.1 trillion [101]. While deaths from other major diseases, including heart disease and stroke, have significantly decreased in recent years, deaths from AD increased by 66% between 2000 and 2008 [101]. More than a decade has passed since the first US FDAapproved drugs for the ‘treatment’ of AD were unveiled. Yet, despite intense research efforts, there are currently no disease-modifying drugs that can affect the relentless progression of this devastating disease. New thinking on disease pathogenesis and novel therapeutic approaches are urgently needed. Currently, there are two classes of drugs that are FDA approved and prescribed for the treatment of AD: acetylcholinesterase inhibitors and N-methyl-d-aspartic acid (NMDA) receptor antagonists. Cholinesterase inhibitors inhibit the activity of the primary enzyme (acetylcholinesterase) that degrades acetylcholine, thus preserving levels of this neurotransmitter, which can slow the decline in cognitive function and improve overall well-being in AD patients. Four cholinesterase inhibitors are currently approved by the FDA for the treatment of AD: tacrine, donepezil, rivastigmine and galantamine. Memantine, the fifth FDA-approved drug, is an NMDA receptor antagonist. Excitotoxic