DEGENERATIVE DISEASES AFFECTING THE CEREBRAL CORTEX

Question 1

What are degenerative diseases?

Answer 1

These are diseases of gray matter characterized by the progressive loss of neurons with
associated secondary changes in white matter tracts.

The pattern of neuronal loss is selective,
affecting one or more groups of neurons while leaving others, sometimes immediately adjacent,
intact.

Question 2

As genetic and molecular studies of these diseases have progressed certain shared
features have emerged.

A common theme among the neurodegenerative disorders is the ___________________

Answer 2

presence of protein aggregates that are resistant to degradation through the ubiquitinproteasome
system.

These aggregates are recognized histologically as inclusions, which often
form the diagnostic hallmarks of these different diseases.

Question 3

The basis for aggregation varies
across diseases.

It may be directly related to an intrinsic feature of a mutated protein (e.g., ___________________),

Answer 3

expanded polyglutamine repeats in Huntington disease

Question 4

a feature of a peptide derived from a
larger precursor protein (_______________),

Answer 4

e.g., Aβ in Alzheimer disease

Question 5

unexplained alteration of a
normal cellular protein (____________________)

Answer 5

e.g., α-synuclein in sporadic Parkinson disease

Question 6

Degenerative diseases differ in terms of the distribution of disease burden and in the specific
neuropathologic findings (e.g., tangles, plaques, Lewy bodies).

They can be grouped using two
approaches:

Answer 6

• Symptomatic/anatomic:
• Pathologic:

Question 7

What is symptomatic/ anatomic group?

Answer 7

based on the anatomic regions of the CNS that are primarily
affected,which is typically reflected in the clinical symptoms (e.g., neocortical
involvement resulting in cognitive impairment and dementia)

Question 8

What is the pathologic approach?

Answer 8

Pathologic: based on the types of inclusions or abnormal structures observed (e.g.,
diseases with inclusions containing tau or containing synuclein)

Question 9

The discussion that follows is primarily based on the first approach (diseases of cortex, basal
ganglia, etc.) with a few exceptions ______________).

Answer 9

(all of the tau diseases and the synuclein diseases are
considered together

Question 10

Degenerative Diseases

Answer 10

• DEGENERATIVE DISEASES AFFECTING THE CEREBRAL CORTEX
• DEGENERATIVE DISEASES OF BASAL GANGLIA AND BRAINSTEM
• SPINOCEREBELLAR DEGENERATIONS
• DEGENERATIVE DISEASES AFFECTING MOTOR NEURONS

Question 11

DEGENERATIVE DISEASES AFFECTING THE CEREBRAL CORTEX

Answer 11

• Alzheimer Disease
• Frontotemporal Dementias
• Frontotemporal Dementia with Parkinsonism Linked to Tau Mutations
• Pick Disease
• Progressive Supranuclear Palsy
• Corticobasal Degeneration
• Frontotemporal Dementias without Tau Pathology