Arctic Aβ selectively increases diffuse deposition of wild type Aβ in APP transgenic mice with the Swedish mutation

• Studies of familial Alzheimer´s disease (AD) suggest that misfolding and aggregation of amyloid-β (Aβ) peptides initiate the pathogenesis, which causes dementia. The Arctic amyloid precursor protein (APP) mutation results in AD, and Arctic Aβ is more prone to form Aβ protofibrils. Here we show that the number of diffuse Aβ deposits, but not amyloid plaques, is increased if tg-ArcSwe mice synthesizing a low level of Arctic Aβ are crossed with plaque-depositing tg-Swe mice. The diffuse deposits in bitransgenic mice, which contain mainly wild type Aβ42, accumulate in regions both with and without transgene expression. The selective increase of a single type of parenchymal Aβ deposit suggest that different pathways of Aβ aggregation lead to the formation of diffuse and compact Aβ deposits in the brain. The raise in diffuse deposits is most likely due to direct physical interactions between Arctic and wild type Aβ42, and not to altered APP processing in young bitransgenic mice. A mixture of Arctic and wild type Aβ42 facilitates the formation of prefibrillar and fibrillar Aβ assemblies, but inhibits the further elongation of Aβ fibrils in vitro. Our findings might have implications to the pathogenesis of patients who are heterozygous for the Arctic mutation. It also further illustrates how Aβ neuropathology can be manipulated in vivo in a manner reminiscent to prion disorders.    

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)

Nyckelord

Alzheimer‘s disease

amyloid-β protein

senile plaque

Arctic mutation

Swedish mutation

immunohistochemistry

Public health science

Folkhälsovetenskap

Geriatrik

Geriatrics

Publikations- och innehållstyp

vet (ämneskategori)

ovr (ämneskategori)