Is Alzheimer's a disease of the white matter?

PURPOSE OF REVIEW: Alzheimer's disease has long been primarily considered a disease of gray matter. However, convergent evidence has suggested that white matter abnormalities are also important components of Alzheimer's disease. We undertook a review of the recent findings of Alzheimer's disease related white matter aberrations identified in patients with Alzheimer's disease and using in-vitro and in-vivo models, and discuss the potential causes of white matter damage in Alzheimer's disease. In doing so, we aim to provide a renewed insight into white matter changes in Alzheimer's disease and related dementias. RECENT FINDINGS: Neuroimaging studies have found that patients with preclinical Alzheimer's disease have widespread white matter abnormalities at a stage similar to those reported in Alzheimer's disease, whereas gray matter structures were relatively intact. In addition, demyelination of the white matter is reported to occur prior to the presence of amyloid-β plaques and neurofibrillary tangles in the presymptomatic stages of Alzheimer's disease. Furthermore, in a mouse model of Alzheimer's disease, axonal disease due to impaired axonal transport was shown to precede and drive downstream production and aggregation of amyloid β peptides. SUMMARY: White matter abnormalities not only represent an early neuropathological event in Alzheimer's disease but may also play an important role in the pathogenesis and diagnosis of Alzheimer's disease.