Increased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis.

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Abstract

Increased APP (amyloid precursor protein) processing causes β-amyloid (Aβ) accumulation in autosomal dominant Alzheimer's disease (AD), but it is unclear if it also affects sporadic Aβ accumulation. We tested healthy controls and patients with mild cognitive symptoms (N=331) in the BioFINDER study, using cerebrospinal fluid (CSF) Aβ40 as a surrogate for amyloidogenic APP processing. We find that levels of brain Aβ fibrils (measured by 18F-flutemetamol PET) are independently associated with high CSF Aβ40 (P<0.001) and APOE ɛ4 (P<0.001). The association between CSF Aβ40 and brain Aβ is stronger in APOE ɛ4-negative than in positive people (P=0.0080). The results are similar for CSF Aβ38 and for a combination of CSF Aβ38 and CSF Aβ40. In conclusion, sporadic Aβ accumulation may be partly associated with increased amyloidogenic APP production, especially in APOE ɛ4-negative subjects. The risk for sporadic AD may consequently depend on increased Aβ production, in addition to decreased Aβ clearance.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Skåne University Hospital
  • University of California
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi
Originalspråkengelska
Artikelnummer10918
TidskriftNature Communications
Volym7
Utgivningsnummer7
StatusPublished - 2016
PublikationskategoriForskning
Peer review utfördJa