Lecture Flashcards
Genetic Risk Factors in AD pathology
- Trisomy 21(APP) - 20s
- Presenilin 1 (chr 14) - late 30s
- Presenilin 2 (chr 1) - early 40s
- APP (chr 21) - 50s
- APOE e4 - 60s
- APOE e3 - 70s
- APOE e2 - 80s
What genes are involved in Increased production of AB-42? (3)
-Presenilin 1 (chr 14)
-Presenilin 2 (chr 1)
-APP (chr 21)
What genes are involved in Decreased clearance of AB-42? (3)
-APOE e4
-APOE e3
-APOE e2
What are “cotton wool” plaques and in what types of AD are they seen?
-diffuse and distinctive large plaques
-Familial AD with PRESENILIN mutations
-ALSO seen in Late-Onset AD
Neurofibrillary Tangles structure (EM finding)
- Major protein present
Two 10-nanometer filaments that are helically wound
- Phosphorylated Tau
Which Braak and Braak stages are typical pathologic stages of clinically advanced Alzheimer’s Disease?
V-VI
Neuritic plaques are by graded by what system?
CERAD
Amyloid extent is documented by what?
That phase
B-amyloid Thal phases.
- Cerebral cortex
- Hippocampus, entorhinal cortex
- Subcortical nuclei, amygdala
- Brainstem nuclei
- Cerebellum
What is the “ABC” system?
NIA/AA 2012 Guidelines:
A - Thal phase (AB)
- 1:1 & 2
- 2: 3
- 3: 4 & 5
B - Braak stage (NFTs)
- 1: I & II
- 2: III & IV
- 3: V & VI
C - CERAD score (NPs)
- 1: sparse
- 2: moderate
- 3: frequent
1/3 of advanced AD brains contain ____________ in the amygdala region in the form of __________________.
Synuclein
Lewy Bodies
TAR DNA-Binding Protein 43 kDA (TDP-43)
1. Function
2. First described?
- Regulator of transcription and RNA processing
- Misfolded TDP-43 was first described in ALS and FTD
What is Limbic Predominant Age Related TDP-43 Encephalopathy (LATE)?
Pattern of TDP-43 +/- Hippocampal Sclerosis
-present in up to 50% of patients > 80 y/o
-Co-morbid AD NP is common but not required
