Neurodegenerative Diseases SDL Flashcards
What are the general features of neurodegenerative diseases?
- Gray matter diseases (neuron cell bodies)
- Usually an accumulation of protein due to problem with certain mechanism in cell
- Selective injury (clinical findings determined from involved area)
- Results in neuron loss and gliosis (scarring in response to injury)
What is the most common cause of dementia?
Alzheimer’s Disease (AD)
What is normally the cause of death from Alzheimer’s (AD)?
- Pneumonia (infections)
- Malnutrition
Describe the course of Alzheimer’s Disease (AD).
- Gradual impairment of cognitive function
- Later disorientation and memory loss
- Eventual immobilization and muteness
What is the histological findings in Alzheimer’s?
- Neurofibrillary tangles and plaques (composed ot tau proteins)
- Result from a cleavage error in β-APP and results in an accumulation of the β-amyloid which forms the plaques/tangles
What is another result of β-amyloid accumulation?
Cerebral Amyloid Angiopathy (CAA)
- β-amyloid also accumulates in blood vessel walls which weakens them
What are some subsequent changes that occur in the neuron (both axon and body) as a result of Alzheimer’s?
- Formation of paired helical filaments
- Hyperphosphorylated tau
- MAP2 (microtubule associated protein) problems
- Ubiquination
- Neuropil threads
What other disease shows neurofibrillary tangles?
Progressive Supranuclear Palsy (PSP) in the brainstem
In Alzheimer’s, where in the brain do neurofibrillary tangles start to form?
- Start in hippocampus and spread along components of limbic system
- Eventually involve neocortex
Which genes increase chances of developing familial or sporadic Alzheimer’s
- Familial
- β-APP (21)
- Presenilin-1 (14)
- Presenilin-2 (1)
- Sporadic
- ApoE4 (19)
- IL-1A & B (2)
(T/F): Essentially all patients with DLB (Dementia with Lewy Bodies) have Parkinson’s.
True. They will have both cortical and substania nigra lewy bodies.
- However, not all Parkinson’s patients have DLB (they might not have cortical LB)
What are the characteristics of Progressive Supranuclear Palsy (PSP)?
- Symptoms:
- Vertical gaze palsy
- Truncal rigidity
- Histology:
- No tau mutations
- Globose neurofibrillary tangles in globus pallidus, substantia nigra, and dentate nucleus
What are the characteristics of Corticobasal Degneration (CBD)?
- Symptoms:
- Extrapyramidal rigidity
- Alien hand
- Sensory cortical dysfunction
- Cognitive decline
- Histology:
- Balooned neurons
- Tau + astrocytes in motor and premotor cortex, basal ganglia, and substantia nigra
What are the symptoms of Parkinsons?
- Tremor (at rest)
- Rigidity (cogwheel)
- Akinesia or bradykinesia (slow movements)
- Postural instability (late)
- Shuffling gate
What are the pathological findings in Parkinsons?
- Loss of substantia nigra dopaminergic neurons
- Lewy bodies in substantia nigra (α-synuclein +)
- Loss of neuromelanin (pigment responsible for substania nigra color)
- Associated with other Lewy body disorders
What are some other causes of Parkinsonism?
- Drugs (especially neuroleptics)
- Trauma (boxers)
- Other basal ganglia and brainstem diseases
Why might neuromelanin be seen microscopically even if a patient has Parkinsons?
- Neuromelanin can remain for sometime in neuropil after neurons have degenerated
- Neuromelanin can still be in the macrophages that are clearing it out
What is Multiple System Atrophy (MSA)?
- α-synuclein + neuronal inclusions
- Involvement of cerebellum, pons, medulla, substantia nigra and striatum
- Glial cytoplasmic inclusions, typically oligodendroglial
What are the subtypes of Multiple System Atrophy (MSA)?
- MSA-P: Parkinsonism-dominant (striatonigral degeneration)
- MSA-C: Cerebellar dysfunction dominant (olivopontocerebellar atrophy)
- MSA-A: Autonomic dysfunction dominant (Shy-Drager syndrome)
What are the characteristics of Huntington’s Disease?
- Large,involuntary movements (chorea)
- Cortical neuron loss and dementia (usually late)
- Trinucleotide repeats (CAG) in huntington gene (Chr 4)
- Atrophy of striate nuclei (cuadate, putamen) and globus pallidus
What the characteristics and subtypes of Spinocereballar Degeneration?
- Involves degernation in the cerebellum, spinal cord, and peripheral nerves
- Results in:
- Cereballar and sensory ataxia, spasticity, sensorimotor peripheral neuropathy
- It is inherited
- There is neuron loss and gliosis
- Subtypes: Spinocerebllar ataxias (SCA), Friedreich’s ataxia (FA), Ataxia telengiectasia (AT)
(T/F): Motor Neuron Disease can involve upper motor neurons, spinal nerve lower motor neurons, or cranial nerve motor neurons.
True.
What are the characteristics of ALS?
- Affects middle-aged adults
- Slowly progressive (approx 5 years)
- Loss of anterior horn motor neurons
- Degeneration of lateral corticospinal tracts
- Muscle atrophy/weakness
- Eventual respiratory muscle involvement and death
What is Infantile Spinal Muscular Atrophy?
- AKA Werdnig-Hoffman Disease
- A degenerative motor neuron disease that affects spinal muscles in infants (more severe than chronic/adult form)
- Death within one year
- Loss of anterior horn motor neurons
