Path of Neurodegenerative Disease (Baumbach)

Question 1

Patterns of neuronal dysfunction that affect the cerebral cortical neurons result in _______. Those that affect the basal ganglia, cerebellum and motor neurons result in various forms of ______ disorders.

Answer 1

dementia; movement

Question 2

accounts for ~40% of all dementias and is the most common cause of dementia in the elderly

Answer 2

Alzheimer’s disease

Question 3

mutations in this gene have been linked with rare familial forms of Alzheimer’s disease, and are associated with the presence of many neurofibrillary tangles in the brain

Answer 3

APP (amyloid precursor protein)

*mutations have also been found in presenillin genes

Question 4

focal, spherical deposits of neuron fragments surrounding a core of amyloid β-protein, often found in the hippocampus and amygdala in Alzheimer’s patients

Answer 4

neuritic plaques

Question 5

normal biological function of this ubiquitously expressed transmembrane protein is unknown, but may involve neurite outgrowth, synaptic plasticity, or cell adhesion

Answer 5

amyloid precursor protein

*mutations lead to gain of function with increased protein production/deposition of Aß42

Question 6

Which of the following statements regarding Amyloid-ß is FALSE?

A. It is formed from a transmembrane protein precursor via cleavage by alpha and gamma secretases
B. It is made by a gene that is located on chromosome 21, causing increased risk of Alzheimer’s in Down sydnrome persons

C. It can be cleaved into a non-pathogenic peptide, depending on the cleavage enzyme

D. It is linked to other genetic risk factors like # of ApoE4 alleles, which also increase risk of Alzheimer’s

E. Even small aggregates of Amyloid-ß may be pathogenic becuase they alter neurotransmission and are toxic to neurons

Answer 6

A. Amyloid-ß is cleaved from APP by ß-amyloid converting enzyme (BACE) and gamma secretase. Cleavage by alpha and gamma secretases liberates a non-pathogenic peptide.

Question 7

Which of the following statements about Neurofibrillary Tangles (NFTs) is FASLE?

A. They are composed of hyperphosphorylated microtubule-polymerizing proteins

B. They are specific to Alzheimer’s disease

C. They are formed as a byproduct of increased presence of Amyloid-ß.

D. They are most commonly found in the entorhinal cortex

Answer 7

B. NFTs are characteristic of Alzheimer’s disease but are found in other degenerative diseases as well

Question 8

clinical presentation of this disease is frontotemporal dementia, preceding memory disturbances, with onset between 45-65 years; least common of all tauopathies

Answer 8

Pick’s disease

*common presenting complaint when frontal lobe is primarily affected is behavioral changes; when temporal lobe most affected, language problems are often the presenting complaint

Question 9

disease that shows ‘knife-edge’ gyri on gross pathology:

Answer 9

pick’s disease

*characteristic histo show’s pick bodies (more sharply demarcated and more basophilic than lewy bodies):

Question 10

pathology of this disease with peak incidence between 55-65 years of age includes loss of pigmented neurons in the subtantia nigra, leading to rigidity, tremor and bradykinesia, and Lewy bodies

Answer 10

parkinson’s disease

Question 11

a definitive diagnosis of Parkinson’s requires this finding below:

Answer 11

Lewy body

*these are intracytoplasmic, eosinophilic, densely packed cores of alpha-synuclein and other proteins inside neurons

Question 12

when dementia sets in within one year of motor symptom onset in Parkinson’s disease, it is given what clinical diagnosis?

Answer 12

Lewy body dementia

*second leading cause of dementia (next to AD)

Question 13

a group of neurodegenerative disorders producing highly variable clinical presenation, but all characterized by alpha-synuclein positive cytoplasmic inclusions

Answer 13

multiple system atrophy

*includes:

• striatonigral degneneration - predominated by parkinsonism
• OPCA - predominated by cerebellar signs
• Shy-Drager syndrome - predominated by autonomic failure

Question 14

brains of patients with this disease will show four-repeat globoid tau tangles, usually in the basal ganglia and brainstem (this is critical for diagnosis)

Answer 14

progressive supranuclear palsy

Question 15

a progressive disorder characterized by degeneration of motor neurons in motor cortex, brainstema and spinal cord; 20% of familial cases show mutation in SOD1 (superoxide dismutase) gene

Answer 15

amyotrophic lateral sclerosis

*most striking finding on gross pathology are thin and gray anterior roots of the spinal cord

Question 16

characteristic histo finding for ALS:

Answer 16

Bunina bodies (small inclusion bodies found in neuronal cells)