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Les troubles de l'esprit
Sub-Topics
Depression and Manic Depression
Anxiety Disorders
Alzheimer’s-type Dementia

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HelpLink : Cortical thickness, MRI, and early Alzheimer's diagnosisLink : Quantifying age-related myelin breakdown with MRI: novel therapeutic targets for preventing cognitive decline and Alzheimer's disease
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Experiment : L'exploration en IRM des démences de type Alzheimer. Que peut-on voir sur un examen de routine ?
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Tool Module : ApoptosisApoptosis (Programmed Cell Death)

CORTICAL ATROPHY IN ALZHEIMER’S

The clinical signs of Alzheimer’s-type dementia can be explained by the areas of the brain that are atrophied in succession by neurofibrillary tangles and the build-up of amyloid plaques.

These two biological markers associated with Alzheimer’s seem to develop synergistically. The neurotoxicity of the amyloid peptide has an impact on all parts of the brain, but in the mild stage of Alzheimer’s chiefly affects the areas around the hippocampus where neurofibrillary tangles appear.

These tangles, which are caused by a pathology of the tau protein, then intensify under the influence of the amyloid peptide dysfunctions.

The neurofibrillary tangles then gradually extend into other parts of the brain in a specific, invariable, hierarchical sequence that is explained by the synaptic connections that these areas make with one another. The tau pathology thus develops along anatomical pathways, and not by passive diffusion.

Neuroscientists have defined 10 stages of tau pathology that correspond to 10 areas of the brain that atrophy in succession (see the graph below). The clinical manifestations of this atrophy generally appear around stage 5, 6, or 7, when the polymodal association cortices, such as the parietal, anterior frontal, and superior temporal cortices, start to be affected.

The weight symbols marked APP* represent the synergistic development of tau protein pathology and amyloid plaques.
Source : www.lille.inserm.fr/u422

The threshold for clinical manifestations certainly varies. It is modulated by many other conditions besides tau and amyloid protein dysfunctions. These conditions include reduced trophic factors, the presence of apoptotic factors (follow the Tool Module link to the left) and microinflammation, astrocytic and microglial reactions, and oxidative stress.

The harmful effects of associated pathologies, such as vascular ones, can also raise or lower this threshold. And, of course, there are other environmental and genetic factors that influence neuronal vulnerability (and hence the “neuronal reserve"), the healthy development of neural networks, etc.

 

Brain imaging does not enable clinicians to diagnose Alzheimer’s or to detect it before the first symptoms appear, but nevertheless is a valuable tool for confirming the diagnosis and understanding the progress of the brain atrophy associated with it.

Promising results have been obtained when classic imaging methods such as positron emission tomography (PET) and magnetic resonance imaging (MRI) have been adapted to the specific characteristics of Alzheimer’s.

For example, PET can be used to visualize the rate of absorption of glucose in various parts of the brain, and thereby detect whether there are any areas that are absorbing less. This information is very useful, because studies have shown that people in the earliest stages of Alzheimer’s absorb less glucose in certain parts of their brains.

PET is also used with the marker PiB (Pittsburgh compound B), a fluorescent molecule that binds to beta-amyloid peptide and can therefore be used to visualize the presence of the amyloid plaques associated with Alzheimer’s disease.

With MRI, one can, for example, observe the atrophying of the hippocampus over time, on the basis of measurements of its volume. Other applications of MRI to Alzheimer’s research have also been developed, such as mapping the build-up of sodium in certain areas of the brain—a phenomenon specific to Alzheimer’s.

Tool Module: Brain ImagingLink : Les pistes de recherche pour mieux comprendre la maladieLink : Pittsburgh compound BExperiment : Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-BLink : Pittsburgh Compound-B Zooms into ViewLink : Une nouvelle technique d'IRM pour une meilleure compréhension des maladies neurodégénératives

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