The Neuropathology of Dementia (14) Flashcards
Limbic system
Arousal, emotion, motivation, attention and memory
Hippocampus
New info is stored, helps concentrate on specific things
Amygdala
Emotions and fiction
Cognition
Sum of brain functions which allows us to integrate in the environment
Intellectual skills
Learning and memory, language, visuospatial skills, emotion, personality
Microcircuits in brain
Neuron > synapse > neurotransmitter > AP
Classification of neurodegenerative disorders
Functional - cognitive (AD)/movement (PD)
Anatomical - frontotemporal dementia (FTB), corticobasal degeneration (CBD)
Etiological - vascular dementia (VaD), prion disease
Proteinopathy - taupathy (AD), a-Synucleionpathy (DLB)
Cognitive disorders
- AD (temporal, parietal and front degeneration)
- Frontal temporal degeneration
- Multifocal degeneration (Cortiocobasal degeneration)
- Cognitive and movement (DLB)
Proteins involved
B-amyloid, Tau, a-synclein, Ubiquitin
B-amyloid
Insoluble fibrous protein aggregates (fibrils), >18 > amyloidosis/degenerative disorders
Tau proteins
Intra-cellular, stabilise microtubules in neurons, 6 isoforms
A-synuclein
Start to globulise > Lewy body, intra-cellular, interferes with RER, mitochondria, ribosomes, seen in PD and DLB
Ubiquitin
Small regulatory proteins found in almost all cells, direct proteins to compartment in cell - proteasome (destroy and recycle proteins, can be attached to and label them), mutation > build up of abnormal proteins and chemicals
Pathogenesis of proteins
- Oxidative stress - free radicals
- Glutamine stimulation
- Apoptosis
- Cytokines - inflammatory response
- Genetic - single gene mutations/multiple
- Age-related decline in efficiency of some metabolic pathways
- Unknown
Accumulation of abnormal proteins (intracellular)
Tau (AD), a-synuclein (DLB), Polyglutamine (HD), Ubiqutin (Pi D)
Accumulation of abnormal proteins (extracellular)
Amyloid (AD)
Macroscopical examination
- Brain weight 900-1100 grams (1200-1400 normal)
- Atrophy in cerebral gyri (hippocampus, temporal, parietal, frontal lobe, cingulate gyrus)
- Atrophy in white matter - thin corpus callous
- Atrophy in deep white matter
- Ventricular dilatation
- Atrophy in brain stem and cerebellum
- Pale substantia nigra and locus ceruleus
Microscopical examination
- Neuron loss from hippocampus, cerebral cortex, SN and LC
- Microvacuolation in cerebral neocortex
- Attenuation in white matter
- Wide perivascular spaces in white matter
- Accumulation of abnormal proteins (amyloid-plaques, tau-neurofibiliary tangles, a-synuclein - Lewy bodies, ubiquitin - pick’s bodies)
Where do plaques start?
In hippocampus and spread out
CERAD plaque densities
Links plaque density with age and clinical symptoms, useful for research (normal, definite AD, probable AD, possible AD)
Macroscopical findings in AD
- Brain weight 900-1200
- Atrophy of gyro, widening of sulci (frontal, temporal, parietal and hippocampus)
- Ventricular dilatation
Microscopical findings in AD
Neuronal loss, NP, NFT and neuropil threads
Macroscopical findings in Dementia with Lewy body (DLB)
- Pale SN and LC
- Atrophy in amygdala, cingulate gyrus, tempora, parietal and frontal lobes
Microscopical findings in Dementia with Lewy body (DLB)
- Neuronal loss from SN and LC
- Accumulation of a-synuclein +ve bodies in neurons of SN, amygdala and later cerebral cortex
Lewy bodies appearance
Bright red bodies inside neurons
Vascular dementia
- Multi-infarct dementia
- Binswanger’s disease
- Arteriolosclerosis
Binswanger’s disease
Infarct in white matter
Arteriolosclerosis
High arterial blood pressure, smooth muscle walls > collagen > infarction
Frontotemporal dementia/Pick’s disease
- Neurons look like balloons
- Picks bodies - Ubiquitin and tau +ve
