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Neuron. 2005 Jul 21;47(2):191-199. doi: 10.1016/j.neuron.2005.06.030.

Abeta42 is essential for parenchymal and vascular amyloid deposition in mice.

Author information

1
Department Neuroscience Mayo Clinic College of Medicine Jacksonville, Florida 32224.
2
Department of Human Genetics Mount Sinai School of Medicine New York, New York 10029.
3
Laboratory of Neurogenetics National Institute on Aging National Institutes of Health Bethesda, Maryland 20892.
#
Contributed equally

Abstract

Considerable circumstantial evidence suggests that Abeta42 is the initiating molecule in Alzheimer's disease (AD) pathogenesis. However, the absolute requirement for Abeta42 for amyloid deposition has never been demonstrated in vivo. We have addressed this by developing transgenic models that express Abeta1-40 or Abeta1-42 in the absence of human amyloid beta protein precursor (APP) overexpression. Mice expressing high levels of Abeta1-40 do not develop overt amyloid pathology. In contrast, mice expressing lower levels of Abeta1-42 accumulate insoluble Abeta1-42 and develop compact amyloid plaques, congophilic amyloid angiopathy (CAA), and diffuse Abeta deposits. When mice expressing Abeta1-42 are crossed with mutant APP (Tg2576) mice, there is also a massive increase in amyloid deposition. These data establish that Abeta1-42 is essential for amyloid deposition in the parenchyma and also in vessels.

PMID:
16039562
PMCID:
PMC1373682
DOI:
10.1016/j.neuron.2005.06.030
[Indexed for MEDLINE]
Free PMC Article

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