Activity-Induced Amyloid-β Oligomers Drive Compensatory Synaptic Rearrangements in Brain Circuits Controlling Memory of Presymptomatic Alzheimer's Disease Mice

Mechanisms by which autophagy regulates memory capacity in ageing

“…Impaired autophagy/lysosomal protein degradation has been associated with the accumulation of misfolded proteins. Therefore, we performed a dot blot analysis to evaluate the presence of amyloid fibrils, using the OC antibody (OC + ) in Tris‐buffered saline (TBS) containing 1% TX‐100 (TBS‐TX) and TBS fractions, which are generally used to evaluate intracellular and extracellular protein aggregate load, respectively (Pignataro et al, 2019). The OC antibody recognizes epitopes common to different types of amyloid fibrils, including those made of Aβ and α‐syn aggregates (Kayed et al, 2007), hereon defined as “amyloid load.” Impaired mice showed a significant TBS‐TX accumulation of OC + amyloid fibrils compared to Preserved mice (Figure 3a).…”

“…We used standard procedures already described in previous studies (Pignataro et al, 2019). See Appendix for details.…”

Early-Occurring Dendritic Spines Alterations in Mouse Models of Alzheimer’s Disease Inform on Primary Causes of Neurodegeneration

“…In vitro evidence that neuronal activity increases the formation and release of Aβ peptides in hippocampal neurons overexpressing APP which then shows impairment in excitatory synaptic transmission (Kamenetz et al, 2003 ) provides a plausible explanatory framework. However, in vivo evidence (Pignataro et al, 2019 ) that cognitive activity enhances Aβ release in the hippocampus of 2-month-old Tg2576 mice and prevents the learning-induced formation of spines in this region indicates that contrary to the beneficial effect of diffuse EE-related sensorial/social stimulation on cognition, focused cognitive activity increases Aβ load in regions supporting high cognitive functions which accelerates the cognitive decline. This aspect should be carefully considered in designing cognitive stimulation protocols aimed at preventing cognitive deterioration at the onset of mild cognitive impairments.…”

Cognitive Reserve in Model Systems for Mechanistic Discovery: The Importance of Longitudinal Studies

“…Shift to non-hippocampal memory systems to compl, ete task (allocentric > egocentric, CA1 > basal ganglia, amygdala activation; Cabeza et al, 2002;Burger et al, 2007;Deipolyi et al, 2008;Grady, 2008;Epp and Galea, 2009;Steffener et al, 2009;Morris et al, 2012;Olvera-Cortés et al, 2012;Steffener and Stern, 2012;Zelikowsky et al, 2013;Snigdha et al, 2017;Cabeza et al, 2018;Pignataro et al, 2019;Smith et al, 2020).…”

“…Several recent animal studies provide descriptions of plastic properties involved in the recruitment of different circuits to compensate for brain aging and pathology of the hippocampus (Zelikowsky et al, 2013;Pignataro et al, 2019). Contextual fear conditioning normally depends on the hippocampus and in an AD model, preserved memory was observed despite a decrease in hippocampal activation (Pignataro et al, 2019). Rather, increased activation and dendritic spine growth were observed in the amygdala.…”