Neurodegenerative disorders Flashcards
Common theme of neurodegenerative disorders
Presence of protein aggregates that are resistant to degradation through ubiquitin-proteasome system
Neurodegenerative disorders affecting cerebral cortex neurons
Alzheimer’s
Pick/FTD
Neurodegenerative disorders affecting basal ganglia
Parkinson’s
Huntington’s
Neurodegenerative disorder affecting spinocerebellar tract
Friedreich ataxia
Neurodegenerative disorder affecting motor neurons
ALS
Genetic mutations associated with early onset Alzheimer’s
PSEN-1 on chromosome 14 (common)
APP on chromosome 21
PSEN-2 on chromosome 1
Genetic mutation associated with late onset Alzheimer’s
ApoE4 on chromosome 19
Brain atrophy of medial temporal lobe and widening of lateral ventricles on MRI
Alzheimer’s disease
Degeneration of cholinergic neurons in basal nucleus and deficiency of choline acetyltransferase resulting in decreased Ach
Alzheimer’s disease
EC neuritic plaques of beta-amyloid protein and IC tau neurofibrillary tangles
Alzheimer’s disease
Enzymatic cleavage of APP by beta-secretase and gamma-secretase leads to production of A-beta peptides to form
Amyloid plaque in Alzheimer’s disease
Alterations in personality, behavior, and speech pattern precede memory loss
Fronto-temporal dementia
Common mutations in fronto-temporal dementia
C9orf72 on chromosome 9 –> TDP-43
GRN on chromosome 7 –> TDP-43
MAPT on chromosome 17 –> Tau
Name used to tau histopathologic fronto-temporal dementia
Pick disease
Ballooned, achromatic cytoplasm with an eccentric nucleus
Pick cells
Clusters of microglial cells/macrophages around small foci of necrotic brain tissue associated with memory loss
Microglial nodules in HIV associated dementia
Gene mutations associated with early onset Parkinson’s
SNCA
GBA
LRRK2
PINK1/Parkin
Cardinal features of Parkinson’s disease
Resting tremor
Cogwheel rigidity
Brady- or akinesia
Gait dysfunction
Intraneuronal proteinaceous inclusions of alpha-synuclein
Lewy bodies
3 stages of DLB
Brainstem predominant
Transitional limbic
Diffuse neocortical
Early onset dementia with hallucinations and parkinsonism
DLB
Autosomal dominant disease with anticipation characterized by decreased GABA and unbalanced dopamine in the striatum
Huntington’s disease
Prominent loss of medium size spiny neurons and gliosis in the caudate nucleus and putamen with intraneuronal inclusions
Huntington disease
MRI findings in Huntington disease
Enlargement of lateral ventricles reflecting atrophy of caudate lobes
Autosomal recessive trinucleotide repeats in the frataxin gene on chromosome 9 causing mitochondrial iron overload
Friedrich ataxia
Conditions associated with Friedrich ataxia
Hypertrophic cardiomyopathy
Kyphoscoliosis
Foot abnormalities
DM
Infant or toddler presents with spastic weakness, staggering gait, and frequent falls with kyphoscoliosis
Friedrich ataxia
Generation of neurons in spinal cord, brainstem, cerebellum, and motor cortex in toddler
Friedrich ataxia
Autosomal recessive mutation in ATM gene
Ataxia telangiectasia
Normal function of ATM gene
Repair of dsDNA breaks
Increased risk of developing in ataxia telangiectasia
Carcinomas
Gliomas
Lymphomas
Most common progressive motor neuron disease
ALS
Mutations associated with familial ALS
C9orf72
SOD1
TDP43 and FUS/TLS
Asymmetric limb weakness, slight spasticity of legs, generalized hyperreflexia, but no incontinence and spared sensation
ALS
Residual motor neurons may contain eosinophilic bunina bodies and ubiquitin rich filamentous aggregates
ALS
Type of mutation in Huntington disease
Trinucleotide repeat of CAG in huntingtin gene
