Vascular dysfunction in Alzheimer disease: cause or consequence?

During the last 10 years, a lot of progress has been made in unraveling the pathogenic cascade leading to Alzheimer s disease (AD). However, some important aspects of the disease mechanism are not yet fully understood. In particular, there is no consensus as yet on whether the disease acts through a loss or a gain of function mechanism (Van Broeck et al, 2007). AD and cerebrovascular dementia are two common causes of dementia and, by present diagnostic criteria, are mutually exclusive using vascular pathology as an arbitrary demarcation in differential diagnosis. However, evidence from epidemiological, neuropathological, clinical, pharmacological, and functional studies suggest considerable overlap in risk factors and pathological changes suggesting shared common pathogenic mechanisms between these two diseases such that vascular factors play a vital role in the pathogenesis of AD (Zhu et al, 2007). AD is associated with considerably decreased cerebral blood flow (CBF) thought to be secondary, since dead neurons do not need oxygen and glucose. This view has been critically re-examined and AD has been re-evaluated by some researchers as a disorder caused by primary and not by secondary CBF deficiency. In fact, some experimental evidence indicates that dysfunction of the neurovascular unit may be an early event in AD and could provide a potential link between this disorder and cerebral ischemia (Iadecola, 2004). This new approach opens new possibilities for treatment and prevention (Niedermeyer, 2006).