Alternative neural circuitry that might be impaired in the development of Alzheimer disease

Abstract

It is well established that some individuals with normal cognitive capacity have abundant senile plaques in their brains. It has been proposed that those individuals are resilient or have compensation factors to prevent cognitive decline. In this comment, we explore an alternative mechanism through which cognitive capacity is maintained. This mechanism could involve the impairment of alternative neural circuitry. Also, the proportion of molecules such as Aβ or tau protein present in different areas of the brain could be important.

Subregional Density of Neurons, Neurofibrillary Tangles and Amyloid Plaques in the Hippocampus of Patients With Alzheimer’s Disease

“…The source of variability may also be attributable to the individual cognitive reserve. Cognitive reserve has been proposed as a compensatory mechanism, which serves as protection against neuronal degeneration, allowing variable numbers of PHF Tau-ir neurons and Aβ -ir plaques to be presented (Tucker and Stern, 2011;Lazarczyk et al, 2012;Steffener and Stern, 2012;Stern, 2012;Avila et al, 2015;Hoenig et al, 2017).…”

Alzheimer’s Disease and Empathic Abilities: The Proposed Role of the Cingulate Cortex

“…This degeneration has two direct and fatal consequences: on the one hand, the connectivity of the hippocampal CA1 is undermined [ 87 ] and, on the other hand, the functionality of the PCC is diminished [ 59, 88 ]. In this way, connections between the cerebral cortex and the CA1 are impaired, either through the EC or through the PCC, leading to loss of memory [ 57 ]. Thus, by looking at the rate of decline of the cingulate cortex and the empathic abilities in the AD continuum, we can glimpse a link between them ( Table 1 ).…”

“…However, not only individual resilience and compensating factors such as cognitive reserve may help to slow down memory loss [ 55, 56 ], but also alternative pathways for connecting the cerebral cortex and CA1 have been recently identified. It has been described an alternative neural circuitry that could delay the transition from a non-demented stage to a mild cognitive impairment (MCI) [ 57 ]. This alternative pathway, that can connect cerebral cortex to CA1 without going through the EC [ 58 ], includes posterior cingulate cortex (PCC), mammillary bodies, and hippocampal CA2.…”

3D Mapping Reveals Network-specific Amyloid Progression and Subcortical Susceptibility

“…Although the MB is a critical part of the Papez long-term memory circuit connecting the hippocampus to the anterior thalamus, 34,51 it has not been strongly implicated in AD. 34,42,52,53 This is somewhat surprising because its major inputs, the subiculum and prefrontal cortex 54 , have been shown to demonstrate significant synaptic loss that correlates with memory performance. 55–58 Furthermore, the MB is part of the head-direction system, a group of critical navigation regions including hippocampus, thalamus, and retrosplenial cortex that are affected in AD, and the pathology in which is thought to underlie spatial memory deficits seen in the disease.…”