Aβ-40 Y10F Increases βfibrils Formation but Attenuates the Neurotoxicity of Amyloid-β Peptide

Aβ-40 Y10F Increases βfibrils Formation but Attenuates the Neurotoxicity of Amyloid-β Peptide

Alzheimer's disease (AD) is characterized by the abnormal aggregation of amyloid-β peptide (Aβ) in extracellular deposits known as senile plaques. The tyrosine residue (Tyr-10) is believed to be important in Aβ-induced neurotoxicity due to the formation of tyrosyl radicals. To reduce the likelihood of cross-linking, here we designed an Aβ-40 analogue (Aβ-40 Y10F) in which the tyrosine residue w...

Amyloid b-Peptide Ab1–42 But Not Ab1–40 Attenuates Synaptic AMPA Receptor Function

The brains of Alzheimer’s disease (AD) patients have large numbers of plaques that contain amyloid beta (Ab) peptides which are believed to play a pivotal role in AD pathology. Several lines of evidence have established the inhibitory role of Ab peptides on hippocampal memory encoding, a process that relies heavily on aamino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function....

Amyloid precursor protein mutation E682K at the alternative β-secretase cleavage β′-site increases Aβ generation†

BACE1 cleaves the amyloid precursor protein (APP) at the β-cleavage site (Met(671) -Asp(672) ) to initiate the generation of amyloid peptide Aβ. BACE1 is also known to cleave APP at a much less well-characterized β'-cleavage site (Tyr(681) -Glu(682) ). We describe here the identification of a novel APP mutation E682K located at this β'-site in an early onset Alzheimer's disease (AD) case. Funct...

Amyloid-β Protofibril Formation and Neurotoxicity Implications for Alzheimer’s Disease

Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation

Alzheimer's disease (AD) is characterized by extracellular plaques in the brain, mainly consisting of amyloid-β (Aβ), as derived from sequential cleavage of the amyloid precursor protein. Epidemiological studies suggest a tight link between hypovitaminosis of the secosteroid vitamin D and AD. Besides decreased vitamin D level in AD patients, an effect of vitamin D on Aβ-homeostasis is discussed...