title: Tau pathology and parietal white matter lesions have independent but synergistic effects on early development of Alzheimer's disease.
abstract: BACKGROUND
  White matter lesions (WMLs) are a common finding in patients with dementia. This study investigates the relationship between WMLs, hyperphosphorylated tau (P-tau) in cerebrospinal fluid (CSF) and apolipoprotein E (APOE) ε4 genotype in prodromal Alzheimer's disease (AD).
  
  
  METHODS
  Baseline levels of tau, P-tau and β-amyloid 1-42 in CSF, the presence of WMLs in the brain, and the APOE genotype were ascertained in 159 patients with mild cognitive impairment (MCI) and 38 cognitively healthy controls.
  
  
  RESULTS
  After 5.7 years, 58 patients had developed AD. In this group, patients with normal levels of CSF P-tau had higher levels of WMLs in the parietal regions than those with pathological P-tau levels (p < 0.05). Also, patients without APOE ε4 alleles had more WMLs in the parietal lobes than those with at least one allele (p < 0.05). MCI patients with pathological P-tau levels and parietal WMLs showed a greater risk of developing AD than those with just one of the two pathological parameters.
  
  
  CONCLUSIONS
  We suggest that WMLs in parietal lobes and tau pathology likely have independent but synergistic effects on the reduction of the cognitive reserve capacity of the brain. In patients with a more low-grade AD pathology, WMLs in the parietal lobes might increase the risk of developing dementia.
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden ; Memory Clinic, Skåne University Hospital, Malmö, Lund, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Hertze
authors.forename: Sebastian
authors.initials: S
authors.lastname: Palmqvist
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson
keywords: Alzheimer's disease; Cerebrospinal fluid; Dementia; Follow-up studies; White matter lesions