Annals of Neurology: Potential therapeutic targets for Alzheimer's disease: posteromedial and anterior temporal networks

The hippocampus is a complex structure connected to two cortical networks, namely the anterior-temporal (AT) and posterior-medial (PM) networks
.

The anterior-lateral part of the entorhinal cortex and surrounding cortex is mainly connected to the AT cortical network, including the anterior ventrolateral temporal cortex, the lateral orbitofrontal cortex, and the amygdala

Gaël Chételat et al.
published a research article in Annals of Neurology, which evaluated the functional changes of the two networks of AT and PM, their changes over time, and the cognition of Alzheimer's disease
.

The study used resting state functional magnetic resonance imaging, cross-sectional and longitudinal research methods to evaluate 53 patients with β-amyloid-positive Alzheimer's disease and 68 healthy elderly patients with MTL connection evaluation
.

First, the functional connections of the posterior-medial and anterior-temporal networks of the control group were compared

The study found that the connection between the patient’s hippocampus and the posterior-medial neural network was reduced, while the connection between several MTL subregions and the anterior-temporal neural network was enhanced
.

The connection between the hippocampus and the posterior-medial neural network is reduced, while the connection between several MTL subregions and the anterior-temporal neural network is increased
.

The connection between the hippocampus and the posterior-medial neural network is reduced, while the connection between several MTL subregions and the anterior-temporal neural network is increased

Compared with healthy elderly controls, the cross-sectional changes in the functional connections of the medial temporal lobe (MTL) subregions in Alzheimer's disease patients
.

The graph of differences between the groups shows that compared with the control group, the connectivity of the patient’s marginal cortex (PRC), parahippocampal cortex (PHC) and hippocampus (HCP) is significantly reduced (blue to white scale) (A) or increased ( Red to yellow scale) (B)

Compared with healthy elderly controls, the cross-sectional changes in the functional connections of the medial temporal lobe (MTL) subregions in Alzheimer's disease patients

The highest standard uptake value ratio (SUVR) area (green) of haloperidol in amyloid-β-positive patients with mild cognitive impairment and AD dementia, and the highest haloperidol in Alzheimer’s disease SUVR area (yellow)
.

The result of increased patient functional connectivity (red, left) overlaps with the area with the highest tau deposition

The highest standard uptake value ratio (SUVR) area (green) of haloperidol in amyloid-β-positive patients with mild cognitive impairment and AD dementia, and the highest haloperidol in Alzheimer’s disease SUVR area (yellow)

The changes in the posterior-medial and anterior-temporal networks are interrelated.

Compared with the control group, the cross-sectional changes of the medial temporal lobe subregions in the patient group are indicated by solid arrows
.

The longitudinal change of the patient from baseline to follow-up is indicated by a dashed arrow

Compared with the control group, the cross-sectional changes of the medial temporal lobe subregions in the patient group are indicated by solid arrows

Over time, the patient's medial temporal lobe (MTL)-posterior-medial (PM) connection weakens, while the MTL-anterior-temporal lobe (AT) connection increases
.
The weakening of the front and back hippocampus (HCP)-PM network connection respectively predicts the increase of the front and back HCP-AT network connection
.
The blue line represents the fitted regression of the linear mixed-effects model
.

Over time, the patient's medial temporal lobe (MTL)-posterior-medial (PM) connection weakens, while the MTL-anterior-temporal lobe (AT) connection increases
.
The weakening of the front and back hippocampus (HCP)-PM network connection respectively predicts the increase of the front and back HCP-AT network connection
.
The blue line represents the fitted regression of the linear mixed-effects model
.

Gaël Chételat et al.
provided a study on the functional connectivity of MTL partitions through cross-sectional and longitudinal analysis of amyloid β-positive patients with Alzheimer's disease
.
This study found for the first time in AD the changes in the connection between AT , PM and MTL over time (the increase in MTL-AT and the decrease in MTL-PM)
.
MTL-PM connection weakening MTL-AT connection strengthening are two interrelated mechanisms
.
Importantly, both MTL-PM and MTL-AT changes are related to AD-related cognitive decline
.
These results reveal the key role of the posterior-medial and anterior-temporal networks in the pathophysiology and clinical symptoms of Alzheimer's disease
.

The change of AT , PM and MTL connection over time (MTL-AT enhanced and MTL-PM weakened)
.
MTL-PM connection weakening MTL-AT connection strengthening are two interrelated mechanisms
.
The change of AT , PM and MTL connection over time (MTL-AT enhanced and MTL-PM weakened)
.
MTL-PM connection weakening MTL-AT connection strengthening are two interrelated mechanisms
.
Changes in MTL-PM and MTL-AT are both related to AD-related cognitive decline
.
Changes in MTL-PM and MTL-AT are both related to AD-related cognitive decline
.

Original source

Longitudinal changes in hippocampal network connectivity in Alzheimer's disease [published online ahead of print, 2021 Jul 19].
Ann Neurol.
2021

Longitudinal changes in hippocampal network connectivity in Alzheimer's disease [published online ahead of print, 2021 Jul 19].
Ann Neurol.
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