• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Potent amyloidogenicity and pathogenicity of Aβ43.

The amyloid-β peptide Aβ42 is known to be a primary amyloidogenic and pathogenic agent in Alzheimer's disease. However, the role of Aβ43, which is found just as frequently in the brains of affected individuals, remains unresolved. We generated knock-in mice containing a pathogenic presenilin-1 R278I mutation that causes overproduction of Aβ43. Homozygosity was embryonic lethal, indicating that the mutation involves a loss of function. Crossing amyloid precursor protein transgenic mice with heterozygous mutant mice resulted in elevated Aβ43, impairment of short-term memory and acceleration of amyloid-β pathology, which accompanied pronounced accumulation of Aβ43 in plaque cores similar in biochemical composition to those observed in the brains of affected individuals. Consistently, Aβ43 showed a higher propensity to aggregate and was more neurotoxic than Aβ42. Other pathogenic presenilin mutations also caused overproduction of Aβ43 in a manner correlating with Aβ42 and with the age of disease onset. These findings indicate that Aβ43, an overlooked species, is potently amyloidogenic, neurotoxic and abundant in vivo.

Pubmed ID: 21725313


  • Saito T
  • Suemoto T
  • Brouwers N
  • Sleegers K
  • Funamoto S
  • Mihira N
  • Matsuba Y
  • Yamada K
  • Nilsson P
  • Takano J
  • Nishimura M
  • Iwata N
  • Van Broeckhoven C
  • Ihara Y
  • Saido TC


Nature neuroscience

Publication Data

August 27, 2011

Associated Grants


Mesh Terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Animals
  • Arginine
  • Cell Line, Tumor
  • Cerebral Cortex
  • Cognition Disorders
  • Disease Models, Animal
  • Embryo, Mammalian
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunoprecipitation
  • Isoleucine
  • L-Lactate Dehydrogenase
  • Male
  • Maze Learning
  • Memory, Short-Term
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Middle Aged
  • Mutation
  • Neuroblastoma
  • Neurons
  • Peptide Fragments
  • Presenilin-1