Dr. Gerhard Multhaup’s group discovered that the amyloid precursor protein cleaving enzyme BACE1 also possesses “amyloidolytic” activity in vivo, whereby larger amyloid peptides (e.g. neurotoxic Aβ42) are commonly degraded into non-toxic Aβ34, a new indicator of amyloid clearance. Such clearance is impaired by ~30% in Alzheimer disease (AD) patients and suggests that impaired clearance is at least as important as increased Aβ production contributing to AD.
We discovered that Aβ40 and Aβ42 are degraded into a common Aβ34 intermediate; Aβ34 levels correlate with the overall Aβ clearance rates in amyloid positive individuals (Liebsch et al., 2019).
In human cerebrospinal fluid, the novel Aβ34/Aβ42 ratio, representing Aβ degradation (Aβ34) and cortical deposition (Aβ42), associated with well-established pre-clinical markers of neurodegeneration.
We are demonstrating that the Aβ34/42 ratio is a specific early marker of AD pathogenesis in humans and currently investigating whether this ratio in plasma may be similarly indicative of AD pathogenesis, thereby enabling cheap and easy identification of asymptomatic persons with early pathology – ideal candidates for AD prevention trials.Novel biomarker for Alzheimer’s Disease