Neurodegenerative Disorders Flashcards
What does cortial degeneration lead to?
Dementia
What does basal ganglia degeneration lead to?
Movement disorders
What does spinocerebellar degernation lead to?
Ataxia
What does moto neuron degeneration lead to?
Upper and lower motor neuron weakness
What are 3 mechanisms in which protein aggregates can cause neurodegernative disease?
Sequester proteins from their normal function; Obstruction of axons by aggregates; Ubiquitin sinks sequestering ubiquitin that cannot be recycled
What is the most common dementia in elderly?
Alzheimer Disease
A brain shows cortical atrophy and Alzheimer Disease is Dx. What changes in the ventricles are seen? What histologic findings can be ssen?
Hydrocephalus ex vacuo; Senile plaques and neurofibrillary tangles
What are the most conspicuous histologic lesions in an Alzheimer brain? Where within the cell are these plaques located?
Neuritic plaques of Beta-amyloid; They’re extracellular!
What are the two major lesions found in Alzheimer Disease?
Neurofibrillary tangles and neuritic plaques
What are neurofibrillary tangles made of? Where are they located in Alzheimer Disease?
Tau protein; Intracellularly
A histological section of an Alzheimer brain shows the following morphology. What is this structure? What is the relationship betwixt this structure and Alzheimer Disease?
Intracytoplasmic Neurofibrillary Tangle; The sites and degrees of distribution of NFTs correlates with clinical Syx;
What chromosomal abnormality is associated with Alzheimer Disease?
Trisomy 21
What larger protein is cleaved to form ABeta?
APP
Mutations in what three genes result in increased risk of Alzheimer disease?
APP, Apoliporpotein E, and Presenilin (PS1 and PS2)
Given the chromosome, name the gene and the Alzheimer disease associated
- 21
- 14
- 1
- 19
- Amyloid Precursor Protein (Early-Onset Familial Alzheimer Disease)
- Presenilin 1 (Early-onset familial Alzheimer Disease
- Presenilin 2 (Volga German Familial Azheimer Disease)
- Apolipoprotein E (epsilon4 allele increased risk of both inherited and sporadic forms of late-onset Alzheimer Disease)
A previously intelligent and reserved man has become disruptive and inappropriate over the past 3 years. He expires. What type of degeneration did he likely experience? What are typical lesions of a brain with this disorder?
Pick Disease Complex; Knife-Edge Atrophy of the frontotemporal regions.
A patient expires. Below is a histological section of the patient. The patient had Pick Disease Complex. What are the histological findings?
Pick bodies; Intracytoplasmic intraneuronal aggregates of tau protein.
A patient is found to have intracytoplasmic Alpha-synuclein. What disease does he have? What is his clinical presentation? What part of the brain is primarily affected?
Lewy Body Dementia; Fluctuating daily cognitive function; Cingulate Cortex
What is the triad that is commonly seen in Parkinson Disease?
Difficulty initiating and sustaining voluntary movement, resting tremor and postural instability
What are the prototypical bradykinetic and hyperkinetic basal ganglia degeneration diseases?
Parkinson and Huntington, respectively
Describe the typical presentation of a person with Huntington Disease
Involuntary rapid twitching movements (chorea) and writhing dance-like movements (athetosis)
Where is there loss of pigmentation in a Parkinson brain?
In the substantia nigra and locus coeruleus
Below is a histologic section of a Parkinson brain. What is the artifact shown below? What is within it?
Lewy Body; Alpha-synuclein
What is MPTP? What can it cause?
It is a contaminant of illicit meperidine synthesis which is metabolized by the brain’s MAO creating a free radical that damages the brain; It causes parkinsonism
What is Multiple System Atrophy?
Filamentous Alpha-synuclein inclusions (glial cytoplasmic inclusions) accumulate in oligodendroglia
What are the hallmarks of Progressive Supranuclear Palsy (PSP)? What are the inclusions?
Atrophy of the midbrain tegmentum leading to exaggerated contribution of the cerebral peduncles to the profile of the midbrain in axial sections resulting in parkinsonism and verticle gaze dysfunction; Tau-rich NFTs!
A patient expires and the brain autopsy is shown below. The caudate nuclei show atrophy and the lateral ventricles are enlarged. What is your Dx? At what age were Syx likely seen? What age did this patient likely die?
Huntington Disease; 40 yo; 55 yo (life expectancy following onset of Syx is 15 y)
What gene is mutated in Huntington Disease? What type of mutation? What determines severity of the disease?
Huntingtin; CAG repeat toxic gain of function mutation; Inherited from father causes greater severity of diease, the greater the number of repeats, the worse the phenotype
What is the most common cause of mental rtardation in boys? What is the most common adult onset muscular dystrophy? What is the most common hereditary spinocerebellar ataxia? What do they all have in common?
FXS; Myotonic Dystrophy; Friedreich Ataxia; They are all nucleotide expansion syndromes
A 25 yo patient presents with ataxia of both the upper and lower limbs, dysarthria, lower limb areflexia, extensor plantar reflex and sensory loss. Below is what his spinal cord looks like! What is the Dx? What is demyelinated in this disease? What type of ataxia is this?
Friedreich ataxia; Dorsal columns, lateral corticospinal tract, spinocerebellar tract; Inflow ataxia
What type of inheritance is Friedreich Ataxia? What gene is mutated? What type of mutation? What determines disease severity?
Autosomal recessive; Frataxin; Unstable Expansion of trinucleotide GAA; The number of trinucleotidee repeats
A patient presents claiming that they had left hand weakness and muscle wasting. He also stated that he had muscle twitches. Although his speech becomes unintelligible and breathing becomes difficult, his intellectual capacity remains the same. Shown in the image is his spine. What is your Dx?
Amyotrophic Lateral Sclerosis;
What mutation occurs in ALS? What neurons are affected in ALS? What is the defining histologic change in ALS?
Missense mutation in the gene that codes for cytosolic Superoxide Dismutase; Lower Motor Neurons, Anterior Horn Cells of Spinal Cord, Motor Nuclei of Brainstem, UMN of cerebral cortex; Loss of large motor neurons and mild gliosis
What disease is caused by a loss-of-function mutation of a neuronal apoptosis inhibitor protein resulting in neurons having an extremely low threshold for initiating programmed cell death?
Spinal muscular atrophy (Werdnig-Hoffman Disease)
