Maggie High

OT 5003
Dr. Baxter
Grand Rounds assignment
On October 24, I attended a Grand Rounds titled Alzheimers Disease
Neuropathology: Horses & Zebras. The speaker was Alberto Serrano Pozo, MD PhD
from the department of Neurology at the University of Iowa Hospitals & Clinics.
He began his presentation by explaining that the two main characteristics of Alzheimers
Disease are amyloid plaques, or waxy proteins, and neurofibrillary tangles. These
markers are always found in the brains of Alzheimers patients and are the positive signs
in the pathology of the disease. The negative signs in the pathology of Alzheimers
include neuron and synapse loss (A.S. Pozo, personal communication, October 24, 2014).
Alzheimers Disease has a high prevalence, and progressively gets worse as time
goes on ("Alzheimer's Disease & Dementia | Alzheimer's Association", 2014). It affects
6% of people above the age of 65 and almost 50% of people above the age of 80 (A.S.
Pozo, personal communication, October 24, 2014). The risk factors for Alzheimers
Disease that Dr. Pozo identified were aging, cardiovascular degeneration, brain trauma,
and APOE-e4. APOE-e4 is a gene, and individuals who inherit it have a greater risk of
developing this disease. Even though aging is the biggest risk factor for the disease,
Alzheimers is not included in the natural aging process ("Alzheimer's Disease &
Dementia | Alzheimer's Association", 2014). The clinical continuum of Alzheimers
disease begins with an individual complaining of memory loss, and the patient will suffer
from mild cognitive impairments. They will still be able to function normally but doctors
can see deficits in neuropsychological tests. Finally, this individual will then begin to

experience dementia symptoms and lose the ability to function normally (A.S. Pozo,
personal communication, October 24, 2014).
According to the presentation, there are a few important dates for the clinical
history of Alzheimers Disease. In 1984, the disease was divided into Possible
Alzheimers Disease, Probable Alzheimers Disease, and Definite Alzheimers
Disease. In 1999, the concept of MCI (mild cognitive impairment) was developed by Dr.
Peterson at the Mayo Clinic. In 2011, the NIA-AA (National Institute on Aging
Alzheimers Association) said that Dementia is due to Alzheimers Disease and that
MCIs were due to Alzheimers Disease and preclinical Alzheimers Disease (A.S. Pozo,
personal communication, October 24, 2014).
The final part of the presenters timeline was concerned with the
Neuropathological aspects of the disease. In 1985, Zaven Kachaturian studied amyloid
plaques in and neurofibrillary tangles in the brain and came up with a criterion that
requires that the number of these risk factors increase with age and meet a certain
threshold. In 1991, the CERAD criteria for neuritic plaques and the Braak criteria for
staging of neurofibrillary tangles were established and six years later, the NIA-RI
combined these criteria in order to classify the likelihood for an Alzheimers diagnosis
into low, intermediate, and high (A.S. Pozo, personal communication, October 24, 2014).
In the 2005-2012 NACC autopsy cohort, researchers excluded patients with other
neurological primary pathologies; subjects whose cognitive impairments might have been
due to alcohol use, depression, medication use, or medical illness; subjects younger than
50; and restricted the study to subjects who had a cognitive evaluation within two years
before the time of their death. The final number was 835 autopsies. The raw data results

showed that less than 1% of the patients had frequent neuritic plaques and were still
cognitively intact and that more than 99% were cognitively impaired. Only 59% were
found to have the lowest degree of pathology and still be cognitively intact. Finally, 41%
of the subjects had some degree of cognitive impairment that was caused by something
else and was not ascribed to Alzheimers Disease (A.S. Pozo, personal communication,
October 24, 2014).
It has been found that both neuritic plaques and neurofibrillary tangles correlate
with the level of cognitive impairment throughout the clinical continuum of Alzheimers
Disease but the clinical-pathological continuum is modified by concurrent pathologies,
such as moderate or severe cerebral amyloid angiopathy or severe small vessel disease,
and education. Also, it was found that 15% of patients with a clinical diagnosis of mildto-moderate Probable Alzheimers Disease had insufficient ADNC (Alzheimers Disease
Neuropathologic Change) and that the APOE-e2 and APOE-e4 genes do not have direct
effects on cognition but influence cognition through their effects on Alzheimers Disease
pathologic changes. Finally, the more advanced Alzheimers cases have cerebral amyloid
angiopathy, neuritic plaques, neurofibrillary tangles, small vessel disease, and
hippocampal sclerosis (A.S. Pozo, personal communication, October 24, 2014).
All in all, this was a very informational presentation and the speaker was able to
clearly convey his vast knowledge of Alzheimers Disease to his audience. Although it
was only an hour long, Dr. Pozo was able to thoroughly explain his topic. His research
efforts, as well as the research of his colleagues, could eventually bring about improved
treatment options for Alzheimers.

References
Alzheimer's Disease & Dementia | Alzheimer's Association. (n.d.). Retrieved
November 8, 2014.