Pathophysiology: Alzheimer's Disease
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Transcript of Pathophysiology: Alzheimer's Disease
Alzheimer’s Disease
Brian J. Piper, Ph.D., M.S.
October 24, 2012
PiB PET scan
Disease Identifier Frequency in US Genetic Patho-physiology
Neurochem
PharmManagement
Parkinson’s JamesParkinson1817
500 K low nigra-striatal
DA common
Alzheimer’s AloysiusAlzheimer1906
5.4 million moderate diffusecortex
ACh? common
Huntington’s GeorgeHuntington1872
30 K high striatum ? uncommon
ALS JeanMartinCharcot
25 K low motorneurons
Glut? common
ACh: acetylcholine; DA: dopamine; Glu: glutamine; sym: symptom management
Neurodegenerative Disorders
Aloysius ”Alois” Alzheimer
• German psychiatrist• Described symptoms + pathology
– Neuronal loss– Plaques– Tangles
• Presentation to SW German Psychiatrist meeting about Auguste Deter ignored butEmil Kraeplin
Cipriani et al. (2011) Neurological Sciences, 32(2), 275-279.
1864-1913
1st, but possibly, atypical case Auguste Deter, 1851-1906
Alzheimer’s Prevalence
Year Patients (millions)
2010 5.8
2020 6.8
2030 8.7
2040 11.8
2050 14.3
Dementia cases in U.S.
Qui et al. (2009). Dialogues in Clinical Neuroscience, 11(2), 111-128.
Healthy Alzheimer’s Disease
AD, coronal cross section
AD, external aspect
AD ≠ Aging
Smith & Jobst (1996). British Medical Bulletin, 52(3), 575-586.
Rate of Decline
Smith & Jobst (1996). British Medical Bulletin, 52(3), 575-586.
Alzheimer’s Disease (AD)
• nucleas basilis is one region affected early• somas for acetylcholine system
Stahl (2008). Essential Psychopharmacology. p. 921.
Genetic Risk Factors
• Late Onset AD• Apolipoprotein E:
– Chromosome 19– 299 amino acids– E3 > E2 > E4
Isoform 112 158
E2 Cysteine Cysteine
E3 Cysteine Arginine
E4 Agrinine Agrinine
Apolipoprotein E & Alzheimer’s Disease
• ε4– 1 copy: 2.5x– 2 copies: 7x
Corder et al. (1993). Science, 261, 921-3.
Test of Neurocognitive Function
• Mini-Mental State Exam (MMSE)– Where are we in?– Count backwards by 7 starting with 100– Remember 3 words– Copy drawing
• Executive function
Folstein, Folstein, & McHugh (1975). J Psychiatric Research, 12, 189-198.
Behavior & Brain
Smith & Jobst (1996). British Medical Bulletin, 52(3), 575-586.
Executive Function Test: Tower of London• Developed by Tim
Shallice in 1982 as a simplified version of the Tower of Hanoi
• Test of problem solving which is sensitive to brain damage
Screen shot from Piper et al. (2012). Behavior Research Methods, 44(1), 110-123.
DSM5 Criteria For Neurocognitive Disorder
http://www.dsm5.org/ProposedRevision/Pages/proposedrevision.aspx?rid=421
Amyloid Plaque
• Amyloid Beta Peptide: 40/42 amino acids• Amyloid Plaque: clusters of Beta amyloid +
Pittsburg Compound B (PIB): A Future Diagnostic Biomarker for AD?
Alzheimer’s Vaccine?
• Immunization against AB42 peptide produced antibodies
• MMSE– 30: maximum– 21-24: mild– 10-20: moderate– <9: severe
• Brain versus behavior
Holmes et al. (2008). Lancet, 372, 216-223.
Alzheimer’s Vaccine?
• Immunization against synthetic AB42 produced antibodies
• MMSE– 30: maximum– 21-24: mild– 10-20: moderate– <9: severe
• Brain versus behavior
Holmes et al. (2008). Lancet, 372, 216-223.