Experimental models of AD rely on the expression of rare human familial mutations and often develop Aβ pathology due to an overproduction of Aβ peptides, rather than a failure of endogenous clearance mechanisms.
Other studies report intact autophagy induction, as evidenced by accumulating intermediate AVs (that is, autolysosomes and autophagosomes) containing improperly digested autophagic substrates and lysosomal hydrolase upregulation, indicating a failure of substrate clearance [ 16, 24].
As there is a failure of plaque clearance in the Tg2576 mice, despite the presence of some RARα, we investigated whether it was a reduction in the production of the endogenous ligand, RA, or a problem downstream of the retinoid activation, which was responsible.
We propose that a failure of macrophage-mediated clearance of fibrin may be the cause of RCM formation after collagen-based hydrogel implants and that mesenchymal stem cell therapy promotes clearance of fibrin and prevents RCM formation.
Tg-SwDI mice may have morphological changes in the endothelium and in the basement membranes of capillaries and arteries, leading to a failure of the mechanisms of clearance of Aβ and other metabolites.
How a failure of mitochondrial transport and clearance leads to gradual neuronal loss still remains to be explored, but it is possible that it induces a modest but persistent disruption to the cellular energy capacity, and this affects specific cellular processes such as synaptic transmission and axonal transport that would eventually lead to neuronal dysfunction and death.
In a random-effects meta-analysis, ciclopirox produced failure of clearance of 21% (RR 0.79, 95% CI 0.67 to 0.94; I² = 81%) (Analysis 19.1).
There is delayed early neutrophil recruitment, failure of clearance of necrotic fibres and a prolonged inflammatory infiltrate that correlates with a delay in the recovery of contraction force.
At 14 days, the difference in the regenerative process between the two strains appeared more to relate to failure of clearance of necrotic tissue than the ability to form new desmin positive fibres.
In populations of people with Down syndrome who develop dementia and in those with early-onset Alzheimer's dementia, the characteristic brain lesions are hypothesised to develop because of various mechanisms leading to the overproduction of toxic changes and deposits, whereas in the older groups with Alzheimer's disease there is predominance for failure of clearance mechanisms.
