| First Author | Liebsch F | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 2240 |
| PubMed ID | 31110178 | Mgi Jnum | J:275557 |
| Mgi Id | MGI:6305596 | Doi | 10.1038/s41467-019-10152-w |
| Citation | Liebsch F, et al. (2019) Abeta34 is a BACE1-derived degradation intermediate associated with amyloid clearance and Alzheimer's disease progression. Nat Commun 10(1):2240 |
| abstractText | The beta-site APP cleaving enzyme 1 (BACE1) is known primarily for its initial cleavage of the amyloid precursor protein (APP), which ultimately leads to the generation of Abeta peptides. Here, we provide evidence that altered BACE1 levels and activity impact the degradation of Abeta40 and Abeta42 into a common Abeta34 intermediate. Using human cerebrospinal fluid (CSF) samples from the Amsterdam Dementia Cohort, we show that Abeta34 is elevated in individuals with mild cognitive impairment who later progressed to dementia. Furthermore, Abeta34 levels correlate with the overall Abeta clearance rates in amyloid positive individuals. Using CSF samples from the PREVENT-AD cohort (cognitively normal individuals at risk for Alzheimer's disease), we further demonstrate that the Abeta34/Abeta42 ratio, representing Abeta degradation and cortical deposition, associates with pre-clinical markers of neurodegeneration. We propose that Abeta34 represents a marker of amyloid clearance and may be helpful for the characterization of Abeta turnover in clinical samples. |
