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

Mattsson, N
Insel, PS
Palmqvist, S
Stomrud, E
van Westen, D
Minthon, L
Zetterberg, H
Blennow, K
Hansson, O

Publication date

March 2016

Publisher

NATURE PUBLISHING GROUP

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 conclu...