Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

Citation: Souza INO and De-Souza EA (2016) Commentary: Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy. A commentary on Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy With incubation time ranging from 5 to 40 years, Creutzfeldt-Jakob disease (CJD) is a deadly condition caused by the accumulation of toxic forms of the prion protein in the brain. Between the 50 s and 80 s, hundreds of patients developed CJD after being treated with cadaveric human growth hormone (c-hGH) contaminated with prion protein. This has led several countries to develop cohorts in order to follow these patients and understand the burden of prion disease in their lives over time. Multiple studies were published linking amyloid-β (Aβ) deposits in the brain—a key feature of Alzheimer's disease (AD)—to prion disease patients that acquired it through several different both Aβ deposits and prion protein deposits occurs by a nucleation-dependent polymerization process in which oligomeric " seed " proteins trigger the formation of an ordered nucleus that may rapidly grows into larger polymer fibrils (Harper and Lansbury, 1997). Recently, Jaunmuktane et al. (2015) performed an autopsy study providing evidence of a possible prion-like transmission of the amyloid-β protein in prion disease patients. The work evaluated brain tissue from 8 patients that died between 36 and 51 years of age of iatrogenic CJD (iCJD) and found abnormal levels of Aβ protein in 7 of them. Such findings were intriguing since age-matched patients with different kinds of prion disease showed extremely rare occurrence of Aβ deposits, engaging researchers in a deeper investigation on the relationship between prion and Aβ proteins. First, the authors excluded any genetic predisposition that these patients might have for several neurodegenerative diseases, including AD, amyotrophic lateral sclerosis, frontal temporal dementia and Parkinson's disease, screening for variations in ApoE and 16 other alleles. Such extensive screening wasn't performed in similar past studies (Hainfellner et al., 1998; Irwin et al., 2013). None of these patients presented causal mutations, but three of them presented possible risk factor alleles for frontotemporal dementia/AD (patient 4) and frontotemporal dementia (patients 6 and 8). Although Aβ deposits are not common in frontotemporal dementia, these patients were the ones presenting widespread cortical and leptomeningeal cerebral Aβ angiopathy. Anyhow, considering the large controversy relating genetic risk factors other than ApoE and actual AD development, such minor mutations seem negligible in the presented scenario. Dissecting amyloid-β Human …