pathophysiology: alzheimer's disease
DESCRIPTION
This presentation was given to first year pharmacy students as part of course on medical physiology and pathophysiology.TRANSCRIPT
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.