Many drugs that target amyloid-β (Aβ) in Alzheimer disease (AD) have failed to demonstrate clinical efficacy. However, four anti-Aβ antibodies have been shown to mediate the removal of amyloid plaque from brains of patients with AD, and the FDA has re
Nanoparticle-based delivery of p16ink4a siRNA reduced amyloid plaque formation and the number of aged microglia surrounding the plaque and reversed learning deterioration and spatial memory deficits. We propose that downregulation of p16ink4a in microglia is a promising strategy for the treatment of ...
et al. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model. Nat. Commun. 10, 3758 (2019). Article PubMed PubMed Central Google Scholar Shankar, G. M. et al. Amyloid-β protein dimers isolated directly from Alzheimer’s ...
However, four anti-Aβ antibodies have been shown to mediate the removal of amyloid plaque from brains of patients with AD, and the FDA has recently granted accelerated approval to one of these, aducanumab, using reduction of amyloid plaque as a surrogate end point. The rationale for approval...
The analysis also showed robust amyloid plaque reduction and slowing of tau accumulation, as measured using PET, in patients treated with donanemab.
Neuroinflammation is thought to contribute to the pathogenesis of Alzheimer’s disease (AD), yet numerous studies have demonstrated a beneficial role for neuroinflammation in amyloid plaque clearance. We have previously shown that sustained expression of
In sporadic, late-onset AD, there is little evidence for increased A production, suggesting that decreased elimination from the brain may contribute to elevated levels of A and plaque formation. Efflux transport of A across the blood-brain barrier (BBB) contributes to A removal from the brain....
immunotherapy, we treated transgenic mice expressing human amyloid precursor protein (APP) carrying the Swedish mutation (KM670/671NL; APP23) with the A??-antibody ??1 or phosphate-buffered saline (PBS) beginning 1) at 3months, before the onset of dendrite degeneration and plaque deposition, ...
Co-administering antibodies to the Aβ N-terminus prevented the LTP and LTD deficits, whereas antibodies to the midregion or C-terminus were less effective. Insoluble amyloid plaque cores from Alzheimer's disease cortex did not impair LTP unless they were first solubilized to release Aβ dimers,...
from the surrounding tissue stands out as very critical. Chemical purification methods using harsh conditions may remove too much of the plaque associated components while common methods such as laser capture microdissection (LCM) would include everything within the specified area. The problems can, ...