Title:Pyroglutamate-Modified Amyloid Beta Peptides: Emerging Targets for Alzheimer´s Disease Immunotherapy
Volume: 11
Issue: 5
Author(s): Roxanna Perez-Garmendia and Goar Gevorkian
Affiliation:
Keywords:
Alzheimer´s disease, amyloid-beta, glutaminyl cyclase, immunotherapy, N-terminal truncated amyloid beta,
pyroglutamate-modified amyloid-beta.
Abstract: Extracellular and intraneuronal accumulation of amyloid-beta (Aβ) peptide aggregates in the brain has been
hypothesized to play an important role in the neuropathology of Alzheimer’s Disease (AD). The main Aβ variants
detected in the human brain are Aβ1-40 and Aβ1-42, however a significant proportion of AD brain Aβ consists also of Nterminal
truncated species. Pyroglutamate-modified Aβ peptides have been demonstrated to be the predominant
components among all N-terminal truncated Aβ species in AD brains and represent highly desirable and abundant
therapeutic targets. The current review describes the properties and localization of two pyroglutamate-modified Aβ
peptides, AβN3(pE) and AβN11(pE), in the brain. The role of glutaminyl cyclase (QC) in the formation of these peptides
is also addressed. In addition, two potential therapeutic strategies, the inhibition of QC and immunotherapy approaches,
and clinical trials aimed to target these important pathological Aβ species are reviewed.
