Neurodegenerative Diseases Causing Degeneration or Loss of Nerve Cells in the Brain
Alzheimer's, Parkinson's, and Huntington's diseases are the neurodegenerative disorders that cause degeneration or loss of nerve cells in the brain. 1
Characteristics of Neurodegenerative Diseases
Neurodegenerative diseases comprise a spectrum of heterogeneous pathologies characterized by:
- Progressive dysfunction, degeneration, and death of neurons
- Incurable and debilitating conditions
- Age-related onset (typically after 40 years)
- Gradual progression of symptoms
Common Pathological Mechanisms
These diseases share several molecular and cellular pathologies:
- Mitochondrial dysfunction
- Protein aggregation
- Glutamate toxicity
- Calcium load
- Proteolytic stress
- Oxidative stress
- Neuroinflammation
- Aging-related processes 2
Specific Neurodegenerative Diseases
Alzheimer's Disease
- Characterized by impaired activity of respiratory chain Complex IV 1
- Shows hypometabolism in the medial frontal and anterior cingulate cortices
- Progressive loss of neurons in the cortex, hippocampus, and basal forebrain
- Development of neurofibrillary tangles and senile plaques 3
- Manifests as progressive cognitive decline and memory impairment 1
Parkinson's Disease
- Characterized by reduced expression and impaired activity of respiratory chain Complex I 1
- Selective degeneration of dopaminergic neurons in the substantia nigra
- Development of Lewy bodies containing neurofilament antigens 3
- Manifests as tremor, rigidity, bradykinesia, and postural instability
- Axial rigidity more prominent than appendicular rigidity 4
Huntington's Disease
- Characterized by impaired activity of respiratory chain Complexes II and III 1
- Selective vulnerability of striatal neurons
- Genetic disorder with autosomal dominant inheritance
- Manifests as chorea, cognitive decline, and psychiatric symptoms
- Classified as a hyperkinetic movement disorder 1
Diagnostic Approaches
Diagnosis of these neurodegenerative diseases typically involves:
- Clinical assessment of characteristic symptoms
- Neuroimaging studies (MRI, PET)
- Electroencephalographic (rsEEG) measures
- Exclusion of other potential etiologies 1
Imaging Findings
- MRI: Shows patterns of atrophy in disease-specific brain regions
- FDG-PET: Reveals hypometabolism in affected brain regions
- DaTscan (Ioflupane SPECT): Shows decreased radiotracer uptake in the striatum in Parkinsonian syndromes 4
Distinguishing Features from Other Conditions
The diseases that do NOT cause degeneration or loss of nerve cells in the brain include:
- Sepsis
- Chronic kidney disease
- Scleroderma
- Rheumatoid arthritis
- B12 deficiency (causes demyelination but not primary neurodegeneration)
- Myasthenia gravis (autoimmune disorder affecting neuromuscular junction)
These conditions may affect the nervous system through other mechanisms (inflammation, metabolic disturbances, autoimmune processes) but do not primarily cause progressive neurodegeneration.
Clinical Implications
Understanding the specific neurodegenerative processes is crucial for:
- Accurate diagnosis
- Prognosis determination
- Development of potential disease-modifying therapies
- Patient and family counseling
Currently, no disease-modifying treatments are available for these neurodegenerative diseases, highlighting the need for continued research into their underlying pathophysiology 4.