Alzheimer's disease: how does it start?

ABSTRACT

Presently, non-genetic Alzheimer's disease (AD) is wrongly classified as a neurodegenerative disorder. When vascular lesions are present, AD is considered to be a vascular dementia. However, compelling evidence indicates that (AD) is a vascular disorder with neurodegenerative consequences. There is an urgent clinical need to ascertain the true cause of this dementia. In this review, evidence indicating that AD is a vascular disorder comes from a number of different disciplines including studies in epidemiology, pharmacology, neuroimaging, clinical medicine, pathology, physiology and experimental research. This collective evidence also addresses many previously puzzling questions regarding i) past and present treatment failures in AD, ii) strange association of AD risk factors with many vascular-related disorders, iii) parallel lesions, clinical symptoms risk factors and potentially interchangeable treatments present in AD and vascular dementia, iv) historical difficulty in finding neurodegenerative markers to detect AD pre-clinically, and, v) paradoxical pathophysiologic events preceding AD neurodegenerative changes. Re-classifying AD as a vascular disorder would very likely improve the chances of finding a useful treatment for this disorder because clinical study designs could focus on more realistic and relevant pathologic targets than is presently practiced. A short summary of potential new research lines that may provide novel therapy in the treatment and management of AD is discussed.