Neurodegenerative Diseases of the CNS Flashcards
Neurodegenerative disorders are (curable or incurable?) and debilitating conditions which result in ______________ of nerve cells
incurable
progressive degeneration
Neurodegenerative disorders
Many are associated with the _____________ which serve as histologic hallmarks of certain disorders
accumulation of abnormal proteins
Neurodegenerative disorders
The clinical manifestation is usually dictated by the area of the brain affected:
○Cortical neurons - ________
○Basal ganglia - _______
○Cerebellum - ________________
○Cortical neurons - dementia
○Basal ganglia - movement
○Cerebellum - ataxia
Neurodegenerative disorders
Protein Diseases with inclusions
Aβ
TPD-43
α-synuclein
Polyglutamine aggregates
Alzheimer disease
Frontotemporal lobar degeneration; Amyotrophic lateral sclerosis
Parkinsons disease
Huntington disease
Neurodegenerative disorders
Protein Diseases with inclusions
Tau
Alzheimer disease
Frontotemporal lobar degeneration
Parkinsons disease (LRRK2 mutation)
Progressive supranuclear palsy
Neurodegenerative disorders
Protein Diseases with inclusions
______ Alzheimer disease
_____ Frontotemporal lobar degeneration
______ Amyotrophic lateral sclerosis
_______ Parkinsons disease
_______ Huntington disease
Aβ
TPD-43
α-synuclein
Polyglutamine aggregates
Neurodegenerative diseases
_________ disease
_________ disease
_____________________
___________ disease
Parkinson disease
Alzheimer disease
Amyotrophic lateral sclerosis
Huntington’s disease
Most common cause of dementia (senility) is ????
Alzheimer disease
Alzheimer disease
Dementia refers to the effect of a group of brain diseases that result in (short or long?) term and (abrupt or gradual?) decrease in the ability to ______ and _______
Long; gradual
think and remember
Alzheimer disease
Named after ________ who first described it on 1906b
Alois Alzheimer
Alzheimer disease
The incidence when considered by age group:
○___% (65 to 74 years)
○____% (75 to 84 years)
○____% (85 years and above)
3
19
47
Alzheimer disease
Most cases are _______, about 5 - 10% are ______ (may experience early onset of symptoms)
sporadic
familial
Alzheimer disease : Pathogenesis
Accumulation of a peptide ( _______ or ________) in the brain
This peptide is derived from the cleavage of _________________________
Aβ protein
β amyloid
Amyloid Precursor Protein(APP).
Alzheimer disease: Pathogenesis
The APP can be processed in two ways:
○Cleavage by ———- and _______ in a process that ________
○Cleavage by _________ cleaving enzyme and ________ to form Aβ
𝛼 -secretase and γ -secretase
prevents the formation of Aβ .
β site APP
β site APP
γ - secretase
Alzheimer disease
Sporadic: Generation and accumulation of Aβ is said to occur (slowly or rapidly?) with ___________
Slowly
advancing age.
Alzheimer disease
Risk Factors:
Increasing age
Genetic: ______ of apolipoprotein E
The e4 allele is (more or less?) effective.
e4 allele
Apolipoprotein helps breakdown Beta amyloid
T/F
T
Alzheimer’s disease
Familial
Mutations in _____,_______
APP
Gamma secretase
Alzheimer’s disease
Familial: Mutations in ____ or in components of γ - secretase ( ___________ ) is seen in early onset familial cases with increased accumulation of Aβ
APP
presenilin(PS) 1 or 2
Alzheimer’s Disease
AD occurs in almost all cases of Trisomy ——- ( _______ ) who survive beyond ____ years.
This is because the gene encoding_____ is located on chromosome (gene dosage effects).
21
Down’s syndrome
45
APP; 21
Accumulation of Aβ :
○Alter ________
○Toxic to ——————- endings.
○Larger deposits (______) can also lead to neuronal death, ellicit a local inflammatory response, alteration of region-region communication through their mechanical effects on axons and dendrites
neuronal transmission
neurons and synaptic
plaques
The presence of Aβ also leads the neurons to hyperphosphorylate the ————— protein called ——-.
○ With hyperphosphorylation, ____ redistributes from ———- into _______ and _______ and aggregates into ______.
○ This process results in neuronal dysfunction and cell death The anatomic distribution of the _____ and ________ account for the clinical manifestations seen and occur well ahead of the onset of clinical signs and symptoms.
microtubule binding; tau
tau; inside the axon
dendrites and cell bodies
tangles
plaques and tangles
Alzheimer’s disease
The presence of Aβ also leads the neurons to _________ the _______ protein called tau.
○ With ______________, tau redistributes from ___________ into _________ and aggregates into ______ .
○ This process results in neuronal dysfunction and cell death
hyperphosphorylate
microtubule binding; tau.
hyperphosphorylation
inside the axon into dendrites and cell bodies
tangles
Alzheimer’s disease
The __________________________ account for the clinical manifestations seen and occur _________ of the onset of clinical signs and symptoms.
anatomic distribution of the plaques and tangles
well ahead