Matches in SemOpenAlex for { <https://semopenalex.org/work/W2987379711> ?p ?o ?g. }
- W2987379711 abstract "Beta amyloid, Aβ 1-42, originally named as Amyloid A4 protein is one of the most investigated peptides in Neuroscience and has attracted substantial interest since its discovery as the main insoluble fibril type protein in cerebrovascular plaques (Glenner and Wong, 1984, Masters et al.,1985) of Alzheimer`s Disease (AD). Since its discovery, Aβ was regarded per se as a „bad molecule“ from the very beginning, triggering the so called „beta amyloid cascade hypothesis“ (Hardy and Higgins, 1992). This hypothesis ignored any physiological function for steadily generated Aß monomer with normal production and turnover rate (Bateman, R., 2006). Accordingly, pan-Aβ related therapeutic approaches were designed to eliminate or lower all three structural isoforms in parallel: 1. the pre-amyloid monomer, 2. the misfolded oligomer and 3. the final fibril. While we already knew about poor correlations between plaques and cognitive decline quite early (Terry et al., 1991), more importantly, also data for an essential benign physiological role for Aβ monomer at low concentrations were surprisingly not considered to be relevant. Here I describe a different Beta Amyloid Hypothesis, the so called „Beta Amyloid Dysfunction Hypothesis“, which in contrast to the „Beta Amyloid Cascade Hypothesis“ builds on an important physiological role of nascent Aβ monomer in accelerated synaptic trafficking in the vesicle budding process. Disease relevant early Aß pathology starts when the control of the folding process is disturbed leading then to misfolded Aß oligomers. These early species compete with the physiological Aβ monomer and exert their neurotoxicity through promiscuous receptors for sticky oligomer type Aß aggregates. The Beta Amyloid Dysfunction (BAD) Hypothesis is introduced and shown to explain negative clinical results of Gamma secretase - and BACE inhibitors as well as pan-Aβ isotype unselective immunotherapies. This new hypothesis also gives clear guidance to what really needs to be done therapeutically to bring this genetically validated target back into successful clinical testing in Alzheimer`s disease. The BAD hypothesis will need further refinement in particular through more detailed exploration for the role of physiological Aβ monomer." @default.
- W2987379711 created "2019-11-22" @default.
- W2987379711 creator A5077715511 @default.
- W2987379711 date "2019-11-07" @default.
- W2987379711 modified "2023-09-30" @default.
- W2987379711 title "The Beta Amyloid Dysfunction (BAD) Hypothesis for Alzheimer’s Disease" @default.
- W2987379711 cites W1523796948 @default.
- W2987379711 cites W1534001036 @default.
- W2987379711 cites W1586918204 @default.
- W2987379711 cites W1691937795 @default.
- W2987379711 cites W1885793991 @default.
- W2987379711 cites W1964049915 @default.
- W2987379711 cites W1968900405 @default.
- W2987379711 cites W1972839799 @default.
- W2987379711 cites W1977914678 @default.
- W2987379711 cites W1980275843 @default.
- W2987379711 cites W1980314710 @default.
- W2987379711 cites W1983735656 @default.
- W2987379711 cites W1988453500 @default.
- W2987379711 cites W1990752558 @default.
- W2987379711 cites W1991988242 @default.
- W2987379711 cites W1991989649 @default.
- W2987379711 cites W1996037698 @default.
- W2987379711 cites W1998937554 @default.
- W2987379711 cites W2001032146 @default.
- W2987379711 cites W2007047564 @default.
- W2987379711 cites W2007273125 @default.
- W2987379711 cites W2025516399 @default.
- W2987379711 cites W2027397361 @default.
- W2987379711 cites W2032920422 @default.
- W2987379711 cites W2033067082 @default.
- W2987379711 cites W2044162798 @default.
- W2987379711 cites W2046847750 @default.
- W2987379711 cites W2046952010 @default.
- W2987379711 cites W2049167261 @default.
- W2987379711 cites W2056092494 @default.
- W2987379711 cites W2060351135 @default.
- W2987379711 cites W2067214887 @default.
- W2987379711 cites W2075348467 @default.
- W2987379711 cites W2081855136 @default.
- W2987379711 cites W2088129757 @default.
- W2987379711 cites W2088133972 @default.
- W2987379711 cites W2090946801 @default.
- W2987379711 cites W2093104385 @default.
- W2987379711 cites W2093426751 @default.
- W2987379711 cites W2095367777 @default.
- W2987379711 cites W2099390250 @default.
- W2987379711 cites W2100550841 @default.
- W2987379711 cites W2101427823 @default.
- W2987379711 cites W2103440561 @default.
- W2987379711 cites W2109221379 @default.
- W2987379711 cites W2117635180 @default.
- W2987379711 cites W2120320261 @default.
- W2987379711 cites W2124750535 @default.
- W2987379711 cites W2132087224 @default.
- W2987379711 cites W2133019124 @default.
- W2987379711 cites W2133541776 @default.
- W2987379711 cites W2135655560 @default.
- W2987379711 cites W2147391105 @default.
- W2987379711 cites W2149104710 @default.
- W2987379711 cites W2158854213 @default.
- W2987379711 cites W2165581033 @default.
- W2987379711 cites W2166976202 @default.
- W2987379711 cites W2169902596 @default.
- W2987379711 cites W2170589861 @default.
- W2987379711 cites W2171259749 @default.
- W2987379711 cites W2171526610 @default.
- W2987379711 cites W2472592786 @default.
- W2987379711 cites W2510806376 @default.
- W2987379711 cites W2532056566 @default.
- W2987379711 cites W2560801454 @default.
- W2987379711 cites W2564588209 @default.
- W2987379711 cites W2577340531 @default.
- W2987379711 cites W2596231972 @default.
- W2987379711 cites W2599851926 @default.
- W2987379711 cites W2605036205 @default.
- W2987379711 cites W2619640740 @default.
- W2987379711 cites W2794138072 @default.
- W2987379711 cites W2809078375 @default.
- W2987379711 cites W2888033839 @default.
- W2987379711 cites W2895353112 @default.
- W2987379711 cites W2937097483 @default.
- W2987379711 cites W2945016564 @default.
- W2987379711 cites W2960149900 @default.
- W2987379711 cites W4297819239 @default.
- W2987379711 doi "https://doi.org/10.3389/fnins.2019.01154" @default.
- W2987379711 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6853841" @default.
- W2987379711 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31787864" @default.
- W2987379711 hasPublicationYear "2019" @default.
- W2987379711 type Work @default.
- W2987379711 sameAs 2987379711 @default.
- W2987379711 citedByCount "63" @default.
- W2987379711 countsByYear W29873797112020 @default.
- W2987379711 countsByYear W29873797112021 @default.
- W2987379711 countsByYear W29873797112022 @default.
- W2987379711 countsByYear W29873797112023 @default.
- W2987379711 crossrefType "journal-article" @default.
- W2987379711 hasAuthorship W2987379711A5077715511 @default.
- W2987379711 hasBestOaLocation W29873797111 @default.
- W2987379711 hasConcept C126322002 @default.