Corticobasal Degeneration - presentation and Pathology
Parkinsonism + Alien Limb Phenomenon + Asymetric motor signs + Dementia
see ballooned, achromatic neurons
deep gray matter and brainstem
Variant Creutzfeldt-Jakob disease differences from regular CJD?
Younger Age at onset
Longer disease duration
+Florid Plaques: amyloid core surroudnded by spongiosis
PrPsc detectable in lymphoid tissue
MAd Cow Disease
Chronic Traumatic Encephalopathy - what happens and what are symptoms and pathology?
Consequence of repetitive mild TBI (concussions) and get symptoms 8-10 yrs later
Symptoms include irritability, impulsivity, aggression, depression, short term memory loss, and heightened suicidality
See Tau Accumulation in patchy distribution - focal areas of increased tau at the cortical surface and in depths of sulci
Increased reactivity in Amygdala
What do you see in Binswanger's disease - subtype of vascular dementia?
White Matter Degeneration secondary to vascular disease - can look like a Leukodystrophy!!!
See Small Artery Sclerosis
Severe Arteriosclerosis + WM Damage = Binswangers
Lewy Body Dementia - Presentation!!!!!! And patholgy
Presentation: *Fluctuating Cognition - 2nd most common form of dementia
Personality changes, visual hallucinations, and LATER get Parkinsonism
Cortical Disease process occurs first and get Lewy Bodies and Lewy Neurites that are synuclein positive in cortex, brainstem and limbic system
What the heck is CADASIL eh?
Cerebral Autisomal Dominant Angiopathy with Subcortical Infarcts and Leukoencephalopathy
NOTCH 3 Mutation!!!!
See White Matter Degeneration and infarcts
Vascular thickening with PAS+ Deposits
Also present in BV in skin
Synucleinopathies - what's happening there?
What are some examples of them?
See Neurodegeneration + accumulation of Alpha-synuclein
Lewy Body Dementia
Multiple System Atrophy (Alpha-synucliein + Oligodendrocytes)
Pathology in FTD with Parkinsonism?
Pathology in FTD with Motor Neuron disease?
FTD+P = Tau positive Neurofibrillary tangles, Frontotemporal degeneration and degeneration of Substantia Nigra
FTD+ALS = Frontotemporal degeneration and TDP-43+ Inclusions
Progressive Supranuclear Palsy - Presentation and Pathology
PSP = Parkinsonism + Taupathy!!!!!!!
Parkinsonism + Vertical Gaze Paralysis
see Tau+ Neurofibrillary degeneration in neurons AND glia in deep gray matter and brainstem
What are the 3 forms of Vascular Dementia?
Multiple Infarct Dementia
Creutzfeltdt Jakob Disease - Pathology and Presentation
Presentation: Rapidly progressive dementia, Startle Myoclonus, Period Sharp Waves on EEG
-middle age or older
see PrPsc instead of normal Pr (chromosome 19) and get Spongiform degeneration of Gray Matter
Genes involves in Alzheimer's Disease?
Familial Early Onset AD:
Chromosome 21 - (seen with Down Syndrome) Gene for Beta Amyloid Precursor Protein
Chromsome 14 - Presenilin 1
Chromosome 1 - Presenilin 2
Beta-APP is cleaved by beta and gamma secretase encoded for by the Presenilin genes
Late onset AD: Apolipoprotein E4 allele
E4 involved in lipid transport
Multiple System Atrophy - Presentation and Pathology
Parkinsonism (with poor response LDOPA) + Ataxia + Autonomic Failure
***Alpha-synuclein positive OLIGODENDROGLIAL cytoplasmic inclusions
Olivopontocerebellar degeneration (cerebellum and inf olivary nuerons)
Shy-Drager syndrome - pregangionic sympathetic neuron loss - degeneration of intermediolateral cell column of SC
Parkinson Disease = Pathology and genetics
Loss of Da Neurons in Substantia Nigra
See Lewy Bodies (Synuclein positive eosinophilic inclusion with halo around it ) in Substantia nigra
Familial Disease linked to Alpha-synuclein PARK1 Genes
What is Parkinsonism?
Presentation of Rigidity, Bradykinesia, and Tremor
ALS Presentation and Pathology
Muscle WEakness/wasting but cognition preserved (except for 10% also have FTD)
Degeneration of Upper and Lower Motor Neurons
Lower = Neurogenic atrophy of skeletal muscles (Amyotrophy)
Upper = Lateral Column Degeneration ( Wallerian Degeneration)
See Bunina Bodies and TDP43+ inclusions in motor neurons
small percentage of Cu-Zn Superoxide Dismutase Germline Mutations (SOD1)
Clinical PResentation of Alzheimer's Disease?
Pathology of Alzheimer's Disease?
Progressive Memory Loss + Dysfunction in at LEAST one other cognitive domain
See Amyloid plaques (Amyloid beta staining with congo red to see beta-pleated sheets)
see Neurofibrillary tangles with Tau
What are the 3 types of Fronto-temporal Dementia?
General Pathology of FTD?
FTD with Parkinsonism linked to Chromosome 17 (tau)
FTD with motor neuron disease - spectrum of ALS
In general, see atrophy of FT lobes - knife blade atrophy
dementia with lots of accumulations that are non-AD and non-LB
Most common cause of familial FTD and ALS worldwide?
Most sporadic but some from C9orf72 hexanucleotide repeat expansion
Tauapathies - in general what's happening?
What are examples of Taupathies?
See neurodegenerative diseases with accumulation of phosphorylated tau
Tau is a microtubule associated protein on Chromosome 17
Picks Disease and FTD
Progressve Supranuclear palsy
Chronic Traumatic Encephalopathy
Pick Disease PResentation and Pathology
Presentation - Language Dysfunction, Personality changes, Memory Loss
Tau-positive Pick Bodies (rounde dinclusins +tau stain) and Ballooned neurons