One of the hallmarks of Alzheimer's disease is the accumulation of amyloid plaques between nerve cells (neurons) in the brain. Amyloid is a general term for protein fragments that the body produces normally. Beta amyloid is a protein fragment snipped from an amyloid precursor protein (APP). In a healthy brain, these protein fragments are broken down and eliminated. In Alzheimer's disease, the fragments accumulate to form hard, insoluble plaques.Neurofibrillary tangles are insoluble twisted fibers found inside the brain's cells. These tangles consist primarily of a protein called tau, which forms part of a structure called a microtubule. The microtubule helps transport nutrients and other important substances from one part of the nerve cell to another. In Alzheimer's disease, however, the tau protein is abnormal and the microtubule structures collapse.
The global prevalence of dementia is 24 million, and is predicted to double every 20 years until at least 2040. Alzheimer disease is the leading cause of dementia.
There is a view that AD is just aging or “accelerated aging”. The AD brain is qualitatively and quantitatively different from the non-AD brain. Thickness determined by CT.
DAT: Dementia of Alzheimer’s type. CT scans conducted annually.The average rate of atrophy in 47 controls was 1.5% per year, while in 20 subjects with AD it was 15.1% per year!
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Late onset AD is the most common form.
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Some correspondence between MMSE & brain structure.
A diagnosis of Neurocognitive Disorder due to AD may be made if other conditions (cerebrovascular disease, Parkinson’s Disease, Fronto-Temporal degeneration) can be excluded.
Pittsburg compound B for measuring Beta amyloid using PET scans. The University of Pittsburgh team partnered with a team of researchers from Uppsala University in Uppsala, Sweden, to conduct the first trials of this new agent in human research subjects. As this was the second investigational compound of this class sent to Uppsala from the University of Pittsburgh group, it was termed simply Pittsburgh compound-B by the Swedish team, who also abbreviated it as "PiB".
AN1792, Elan Pharmaceuticals vaccine. Antibody production was quite variable.
Note disconnect between amyloid and cognitive levels.
Pathophysiology: Alzheimer's Disease
Alzheimer’s Disease Brian J. Piper, Ph.D., M.S. October 24, 2012PiB PET scan
Neurodegenerative DisordersDisease Identifier Frequency in US Genetic Patho- Neuro Pharm physiology chem ManagementParkinson’s James 500 K low nigra- DA common Parkinson striatal 1817Alzheimer’s Aloysius 5.4 million moderate diffuse ACh? common Alzheimer cortex 1906Huntington’s George 30 K high striatum ? uncommon Huntington 1872ALS Jean 25 K low motor Glut? common Martin neurons CharcotACh: acetylcholine; DA: dopamine; Glu: glutamine; sym: symptom management
Aloysius ”Alois” Alzheimer • German psychiatrist • Described symptoms + pathology – Neuronal loss 1864-1913 – Plaques – Tangles • Presentation to SW German Psychiatrist meeting about Auguste Deter ignored but Emil KraeplinCipriani et al. (2011) Neurological Sciences, 32(2), 275-279.
1st, but possibly, atypical case Auguste Deter, 1851-1906
Alzheimer’s Prevalence Dementia cases in U.S. Year Patients (millions) 2010 5.8 2020 6.8 2030 8.7 2040 11.8 2050 14.3Qui et al. (2009). Dialogues in Clinical Neuroscience, 11(2), 111-128.
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 functionFolstein, Folstein, & McHugh (1975). J Psychiatric Research, 12, 189-198.
Behavior & BrainSmith & 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 damageScreen shot from Piper et al. (2012). Behavior Research Methods, 44(1), 110-123.
DSM5 Criteria For Neurocognitive Disorderhttp://www.dsm5.org/ProposedRevision/Pages/proposedrevision.aspx?rid=421