What are degenerative diseases?
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,
As genetic and molecular studies of these diseases have progressed certain shared
features have emerged.
A common theme among the neurodegenerative disorders is the ___________________
presence of protein aggregates that are resistant to degradation through the ubiquitinproteasome
These aggregates are recognized histologically as inclusions, which often
form the diagnostic hallmarks of these different diseases.
The basis for aggregation varies
It may be directly related to an intrinsic feature of a mutated protein (e.g., ___________________),
expanded polyglutamine repeats in Huntington disease
a feature of a peptide derived from a
larger precursor protein (_______________),
e.g., Aβ in Alzheimer disease
unexplained alteration of a
normal cellular protein (____________________)
e.g., α-synuclein in sporadic Parkinson disease
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
What is symptomatic/ anatomic group?
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)
What is the pathologic approach?
Pathologic: based on the types of inclusions or abnormal structures observed (e.g.,
diseases with inclusions containing tau or containing synuclein)
The discussion that follows is primarily based on the first approach (diseases of cortex, basal
ganglia, etc.) with a few exceptions ______________).
(all of the tau diseases and the synuclein diseases are
- DEGENERATIVE DISEASES AFFECTING THE CEREBRAL CORTEX
- DEGENERATIVE DISEASES OF BASAL GANGLIA AND BRAINSTEM
- SPINOCEREBELLAR DEGENERATIONS
- DEGENERATIVE DISEASES AFFECTING MOTOR NEURONS
DEGENERATIVE DISEASES AFFECTING THE CEREBRAL CORTEX