What are Systems Diseases? 

Diseases where interrelated structures: cortex, deep nuclei and descending tracts degenerate synchronously. 

In what area of the brain does AD neuronal loss predominate? 

Fronto-Temporal Region 

What kind of hydrocephalus is seen in AD? 

Ex-vacuo hydrocephalus 

What are the 3 histopathologic features that characterize AD? 

• Neurofibrillary tangles in the cytoplasm of the neurons. 
• Senile or neuritic plaques w/in the neuropil of the cortex
• Amyloid or Congophilic angiopathy

What are neurofibrillary tangles in AD composed of? 

dense bundles of linear or filamentous material, hyperphosphorylated tau protein, and intertwined 'perihelical filaments' (ultrastructural)

Abnormal, round/oval extracellular structures w/in neuropil of cortex w/ pink center of amyloid & surrounding fragments of axons and dendrites

Senile (Neuritic) Plaques 

What kind of vessel damage is seen in AD and to what other condition in this similar to? 

Cerebral Amyloid Angiopathy: small blood vessels are thickened and hyalinized d/t the abnl protein beta-amyloid --> rupture and intracerebral hemorrhage. 

Similar to changes seen in HTN

Beta-pleated sheet configuration

In what chromosome is the Amyloid Precursor Protein?

Chromosome 21

What chromosomal condition is associated with early development of AD?  

Down Syndrome 

(Trisomy 21)

**the APP gene is also found in chromosome 21

Familial AD is associated with abnormalities in what type of protein and located in which chromosome? 

Apolipoprotein E (ApoE) gene, chromosome 19

The Fronto-Temporal dementia & Parkinsonism linked to chromosome 17 is related to what kind of protein abnormalities?

Tau Protein Gene 

"knife edge" and "walnut brain" are terms used in what neurodegenerative dz? 

PICK's disease (lobar Atrophy)

PICK's disease: profound atrophy of the brain, frontal and temporal lobes, diminished brain weight, gyral atrophy; 'knife edge' atrophy & 'walnut brain'

Pick Bodies: round-to-oval, gray-blue intracytoplasmic inclusion: contain tau protein

Progressive Supranuclear Palsy (PSP) 

characterized by what? 

severe dementia & severe neurologic defects

rigidity and dysequilibrium

superimposed gaze palsies in supranuclear origin

abnormalities in colliculi (tectum)

In Progressive Supranuclear Palsy where is neuronal loss seen? 

Basal ganglia, brain stem: colliculi or tectum related to visual system, substantia nigra, dentate nucleus of the cerebellum

In comparison to AD, Progressive Supranuclear Palsy (PSP) has what shaped of filaments at the ultrastructural level? 

PSP: straight filaments

AD: paired-helical filaments 

What kind of dementia is associated with Corticobasal Degeneration (CBD)?

tau-associated dementia

*also has rigidity ( as Parkinsonism) and jerking movements, and depigmentation of substantia nigra

Which is the only form of dementia with a specific genetic abnormality? 

Huntington's Disease

Huntington's Disease

(characteristics)

familial genetic involvement

profound dementia

rigidity and bradykinesis

hyperkinesia (chorea)

dystonia 

Where is the gene abnormality in Huntington's Disease and what is the name of the protein? 

Chromosome 4

Protein: Huntingtin

The coding region of the HD gene is characterized by? 

Abnormally expanded nucleotide triplet repeats of CAGs

*proportional to early age of onset and severity of dz

In what disease in atrophy of the caudate nucleus and putamen striking? 

Huntington's Disease

Parkinsonism

Clinical syndrome characterized by rigidity, tremor, bradykinesia, interalia, including dz w/ abnormalities of the dopaminergic system

Parkinson's Disease

Gross findings? 

loss of neuromelanin dopaminergic neurons --> Depigmentation of the Substantia Nigra of the midbrain and locus coeruleus of upper pons

What is a characteristic microscopic signature of PD? 

Lewy bodies: round structures, consisting of dark, pinkish-red core, surrounded by a light-pink halo

Diffuse Lewy Body Disease

Clinical Syndrome of PD plus dementia, loss of cortical neurons, and remainder containing Lewy bodies, and may have dementia w/ features of AD

What kind of ataxia is seen in Friedreich's Ataxia? 

Spinocerebellar ataxia

What kind of triplet repeats are seen in Friedreich's Ataxia? 

In addition to ataxia what is found in Friedreich's Ataxia? 

• sensory deficits (degeneration of dorsal columns)
• spastic paresis and + Babinski sign
• Pex Cavus (exss raised arch of foot)
• kyphoscoliosis (abnl curvature of spine)
• cardiomyopathy and diabetes mellitus

Morphology of Friedreich's Ataxia

degeneration of the spinocerebellar and corticospinal tracts in the lateral columns and degeneration of the dorsal columns & dorsal sensory roots 

Is Amyotrophic Lateral Sclerosis a UMN or LMN defect? 

Both UMN and LMN defect

What tracts are affected in ALS?

corticospinal & corticobulbar tracts 

Manifestations of UMN degeneration in ALS

spastic paralysis

+ Babinski sign

pseudobulbar palsy

Manifestations of LMN degeneration in ALS

• flaccid paralysis of the innervated skeletal muscle w/ neurogenic atrophy 
• fasciculations/ visible twitching of muscle 
• atrophy of entire motor unit (LMN, axon and muscle)

How is damaged to the hypoglossal nucleus of the brainstem in ALS manifested? 

neurogenic atrophy of the skeletal muscle of the tongue