1. Under the supervision of miklós jászberényi
The physiopathology of Alzheimer’s disease and other neurodegenerative disorders
Janique de vries
Nejla jounaïdi
Chloe marsollier
Under the supervision of miklós jászberényi

2. NDD: an introduction Definition
Neuro: neurones are affected, not necessarily in the brain but also throughout the whole body.
Degenerative: The pathological processes lead to degeneration of neuronal tissue.
Disease: “A disorder of structure or function in a human, animal, or plant, especially one that produces specific symptoms or that affects a specific location and is not simply a direct result of physical injury” (oxford dictionary).

3. NDD: an introduction
Common pathological processes (e.g. protein misfolding & mitochondrial dysfunction).
Different clinical outcomes.
Photo source : ‪

4. NDD: prevalence
Alzheimer’s disease 2010: 35.6 million people worldwide* 2050: million people worldwide*
Parkinson’s disease >1/1000 people affected in Europe**
Photo source : ‪
* 2010 report of ADI
**European commission site

5. Questions What are the common characteristics of ndd ?
What does the term implies concerning the patient’s prognosis ?

6. Common pathogenic features
Alzheimer’s disease
Genetic factors
Abnormal protein aggregations
Neuroinflammation
Mitochondrial dysfunction
Oxidative stress
Excitotoxicity
Apoptosis
Fronto-Temporal dementia
Prion diseases
Huntington’s disease
Amyotrophic Lateral Sclerosis
Parkinson’s disease
Spino Cerebellar Ataxias …

7. Protein misfolding - Hallmark of NDDs - « Proteinopathies »
Alpha helices  Beta sheets
- Aggregations
Amyloid fibrils  Plaque deposits in CNS
Impairment of cellular processes
Common pathway of aggregation  common mechanism of neurotoxicity
Photo source :

8. Protein misfolding 2 mechanisms : Major consequences :
Spontaneous conformation
Induced conformation
Different :
Brain location
Nerve cells repartition (ECR - ICR - Intra-nuclear)
Major consequences :
Interference with axonal transport
Apoptosis
Gliosis
Inflammation
Mitochondrial dysfunctions
Controversial causal role
Photo source : Nature Reviews - Neuroscience

9. Mitochondrial dysfunction
Failure of OXPHOS  ATP depletion  cell death
Abnormal OXPHOS  ROS  oxidative stress  cell death
Mitochondrial damage  opening of mitochondrial permeability transition pores  loss of membrane potential & pH changes  further compromising of OXPHOS
Release of mitochondrial proteins (SMACs)  binding to apoptosis inhibiting proteins  apoptosis

10. Mitochondrial dysfunction
Photo source : "Role of Protein Aggregation in Mitochondrial Dysfunction and Neurodegeneration in Alzheimer’s and Parkinson’s
Diseases" Hashimoto et al

11. The physiopathology of ALZHEIMER’S DISEASE
And now, an example…
The physiopathology of ALZHEIMER’S DISEASE

12. Aetiologies 2 protein abnormalities: Mitochondrial dysfunction:
Αβ peptides  Senile plaques.
Tau protein  Neurofibrillary tangles.
Mitochondrial dysfunction:
Oxidative stress  Tissue damage.
Decreased glucose metabolism
Photo source : American Health Assistance Foundation

13. Clinical aspects and treatments
Sporadic AD.
Familial AD.
Progressive disease ⬄ Progressive loss of function.
Cognitive and motor impairments.
TREATMENTS
NMDA antagonists.
Cholinesterase inhibitors.
AD = major focus of medical research.
AD = major issue of public health.

14. Common features = therapeutic targets
Conclusion
Common features = therapeutic targets

15. Chloé M. Janique de V. Nejla J.
THANK YOU FOR YOUR ATTENTION !