The AβpE 3‐42 peptide is associated with a higher degree of inflammation than Aβ1‐40 in brains with Alzheimer’s disease.

Abstract

AbstractBackgroundAlzheimer’s Disease (AD) is the most common neurodegenerative disease histopathologically characterized by the presence of neuritic plaques (NPs), extracellular deposits composed of amyloid beta peptide (Aβ) and neurofibrillary tangles (NFTs) composed of tau protein. It has been hypothesized that Aβ promotes synthesis and secretes proinflammatory proteins causing neuronal and endothelial damage in the AD brain. In this context, it is not clear if the truncated Aβ species can be more toxic than the full‐length ones. Therefore, this work aimed to explore the association of the Aβ1‐40 peptide (full length) and AβpE3‐42 (truncated species) with inflammation in the brains of AD patients.MethodWe used postmortem tissue from the temporal cortex of patients with AD and it was analyzed by confocal microscopy using antibodies against the peptide Aβ 1‐40 and AβpE 3‐42, phospho tau and caspase‐5 (inflammatory type caspase). The amyloidogenic plaques AB1‐40 and AβpE3‐42 and their association with the inflammation marker caspase 5 were quantified. In addition, caspase 5 was quantified by western blot (WB) in control brains and those with AD.ResultWe found high caspase‐5 immunoreactivity specifically associated with extracellular Aβ peptide deposits. Interestingly, this caspase 5 is associated preferentially with the truncated Aβ pE 3‐42 peptide. Likewise, caspase‐5 was expressed mainly in brain blood vessels which had Aβ peptide deposits. We did not detect the colocalization of this enzyme with the tau protein. WB assays show increased caspase 5 in AD brains compared to controls.ConclusionIn conclusion, our findings show that the truncated AβpE3‐42 peptide is closely associated with caspase 5, a key enzyme in the inflammation process. This latter may be a specific biomarker of inflammation in AD brains.