, also known as Abeta, is a peptide that varies in length from 39 to 43 amino acids and is processed from the transmembrane protein amyloid precursor protein
(APP) by beta-secretase
(BACE-1) and gamma-secretase. Beta amyloid [1-40], beta amyloid [1-42], and beta amyloid [1-43] peptides result from cleavage of APP after residues 40, 42, and 43, respectively. The aggregation of beta amyloid monomers produces insoluble oligomers and protofibrils. The longer "stickier" forms of beta amyloid, particularly ABeta42
, are known as the main component of amyloid plaques, which are deposits (senile plaques or neuritic plaques) found in the brains of patients with Alzheimer's disease
(AD) (1,2). Research indicates that intraneuronal beta amyloid accumulation may be an important proximal neurotoxic event in the pathogenesis of Alzheimer's disease. Abeta deposits have also been reported in the hearts of AD patients (3).
Pyroglutamate amyloid beta peptides (pGlu-Abeta) are N-terminal truncations in which the N-terminal glutamate
is cyclized to pyroglutamate resulting in pGlu-Abeta (3-40/42 and 11-40/42) (4). This pyrE modification may have a greater propensity to aggregate under physiological conditions and has been implicated as the molecular species responsible for seeding larger oligomers of amyloid beta.
1. Chen GF, Xu TH, Yan Y, Zhou YR, Jiang Y, Melcher K, Xu HE. (2017) Amyloid beta: structure, biology and structure-based therapeutic development. Acta Pharmacol Sin. 38(9):1205-1235. PMID: 28713158
2. De-Paula VJ1, Radanovic M, Diniz BS, Forlenza OV. (2012) Alzheimer's disease. Subcell Biochem. 65:329-52. PMID: 23225010
3. Schaich CL, Maurer MS, Nadkarni NK. (2019) Amyloidosis of the Brain and Heart: Two Sides of the Same Coin? JACC Heart Fail. 7(2):129-131. PMID: 30704604
4. He W, Barrow CJ. (1999) The A beta 3-pyroglutamyl and 11-pyroglutamyl peptides found in senile plaque have greater beta-sheet forming and aggregation propensities in vitro than full-length A beta. Biochemistry. 38(33):10871-7. PMID: 10451383