title: Insights into White Matter Damage in Alzheimer's Disease: From Postmortem to in vivo Diffusion Tensor MRI Studies.
abstract: BACKGROUND
  Alzheimer's disease (AD) has traditionally been considered a disease of the gray matter (GM). However, several pathological and neuroimaging studies provided evidence of white matter (WM) abnormalities in this disease. The advent of diffusion tensor (DT) MRI allowed researchers to study in vivo cerebral WM abnormalities in AD, including the earliest stage of the disease and its atypical variants.
  
  
  OBJECTIVE
  To provide a concise overview of the main neuropathological and DT MRI studies that explored WM damage in AD providing new insights into the underlying pathophysiological mechanisms.
  
  
  RESULTS
  Neuropathological studies revealed that GM and WM changes did not concur regionally in many areas, where well-preserved GM often lay over severely changed WM also in nondemented subjects with an underlying AD pathology. DT MRI studies confirmed in vivo a severe WM involvement in classical and atypical AD variants and in the prodromal stage of the disease. Microstructural WM damage was severer and more distributed than expected on the basis of cortical atrophy in all clinical AD phenotypes.
  
  
  CONCLUSIONS
  AD is characterized by a relevant involvement of the WM as demonstrated by postmortem and in vivo evidence. WM microstructural damage in AD is not always secondary to neuronal loss, suggesting a role of other pathological mechanisms such as prion-like propagation of altered proteins or neuroinflammation. DT MRI offers new insight into AD pathophysiology and, more importantly, new possible targets for future experimental therapies.
authors.affiliation: Neuroimaging Research Unit, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Caso
authors.forename: Federica
authors.initials: F
authors.lastname: Agosta
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D066127:White Matter / Q000473:pathology*