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| First Name: | Vassilis | | Last Name: | Koliatsos | | Title: | Associate Professor | | Advanced Degrees: | M.D. | | Affiliation: | Johns Hopkins University School of Medicine | | Department: | Neuropathology, Neurology, Neuroscience and Psychiatry and Behavioral Sciences | | Street Address 1: | Ross Building Room 558 The Johns Hopkins Hospital | | Street Address 2: | 720 Rutland Avenue | | City: | Baltimore | | State/Province: | MD | | Zip/Postal Code: | 21205 | Country/Territory: | U.S.A. | | Phone: | (410) 502-5172 | | Fax: | (410) 955-9777 | | Email Address: |  |
Disclosure:
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Member reports no financial or other potential conflicts of interest. [Last Modified: 9 June 2003]
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View all comments by Vassilis Koliatsos
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Alzheimer Disease, Tauopathies, Aging Process, Stroke and Trauma, Parkinson Disease
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Neurobiology, Neuropathology, Diagnosis, Animal Models, Apoptosis/Cell cycle, Brain imaging, Neurotransmission, Stem cells
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University, Medical hospital
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Graduated from the University of Athens School of
Medicine in 1982. Received training in Internal
Medicine and Neurology while serving in the Hellenic
Navy. He came to Johns Hopkins Hospital, Dept of
Neurology, as a NATO postdoctoral fellow for the
period 1985-87. He completed training in psychiatry
at Sheppard Pratt Hospital. Entered the junior faculty
ranks in Neurology (JHH) in 1987-1990 and then joined
also Pathology (Neuropathology), where he has been
conducting his research in the Alzheimer's Disease
Research Center ever since. He joined the faculty
at the graduate program in Neuroscience as faculty
in 1991 and joined the department of Psychiatry in
1997. He is presently Associate Professor in
Neuropathology, Neurology, Neuroscience and Psychiatry
and Behavioral Sciences at Johns Hopkins Medical
Institutions. He has been awarded the Leadership and
Excellence in Alzheimer's Disease (LEAD) Award by
the National Institute on Aging in 1991 for his work
on cholinergic neurons, trophic factors and Alzheimer's
disease and the Javits Neuroscience Investigator Award
from the National Institute on Neurological Disorders
& Stroke for his work on Lou Gehrig's disease. His
research focuses on transsynaptic models of cortical
cell death (apoptosis) and the role of anti-apoptotic
treatments and stem cells as therapeutics for Alzheimer's
disease and other neurodegenerative diseases. He also sees patients with a combination of neurological and
psychiatric problems such as patients with head injury
and neurodegenerative disorders.
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1. Koliatsos VE, Nauta HJW, Clatterbuck RE, Holtzman DM, Mobley WC and Price DL: Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey. J. Neurosci. 10:3801?3813, 1990.
2. Koliatsos VE, Clatterbuck RE, Winslow JW, Cayouette MH and Price DL: Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 10:359-367, 1993.
3. Henderson CE, Phillips HS, Pollock RA, Davies AM, Lemeulle C, Armanini M, Simpson LC, Moffet B, Vandlen RA, Koliatsos VE and Rosenthal A: GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle. Science. 266:1062?1064, 1994.
4. Portera?Cailliau C, Hedreen JC, Price DL and Koliatsos VE: Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models. J. Neurosci. 15:3775?3787, 1995.
5. Ehlers MD, Kaplan DR, Price DL and Koliatsos VE: NGF?stimulated retrograde transport of trkA in the mammalian nervous system. J. Cell Biol. 130:149?156, 1995.
6. Capurso SA, Calhoun ME, Sukhov RR, Mouton PR, Price DL and Koliatsos VE: Deafferentation causes apoptosis in cortical sensory neurons in the adult rat. J. Neurosci. 17:7372?7384, 1997.
7. Gustilo MC, Markowska AL, Breckler SJ, Fleischman CA, Price DL and Koliatsos VE: The effects of nerve growth factor on recent memory are mediated via structural changes in septohippocampal cholinergic neurons. J. Comp. Neurol. 405:491-507, 1999.
8. Liu Z, Mouton PR, Gastard M, Verina T, and Koliatsos VE: Estrogens modulate experimentally induced apoptosis of granule cells in the adult hippocampus. J. Comp. Neurol. 441:1-8, 2001.
9. Sheng JG, Price DL, and Koliatsos VE: Hippocampal denervation after entorhinal cortex lesions ameliorates amyloid burden in a transgenic mouse model of Alzheimer's disease. J. Neurosci 22: 9794-9799, 2002.
10. Gastard MC, Troncoso JC, and Koliatsos VE: Caspase-3 activation in the limbic cortex of subjects with early Alzheimer's disease. Ann. Neurol., in press (2003).
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How the brain can signal such a massive death of cortical (and subcortical) neurons?
Since there is no solid evidence (yet) that this is simply the result of amyloid and/or PHF accumulation,
what is the cause and the mechanism of such a pervasive destruction and why are primary cortices spared?
Also, I doubt that AD is one illness in the Oslerian sense, rather a set of phenocopies with probably diverse
admixtures of common causes such as adverse gene properties, age, injury/trauma, small-vessel atherosclerosis,
anoxia/ischemia, etc. This needs to be better conceptualized. |
A systems model to account for cortico-cortical destruction in AD has not been developed,
despite some initial efforts. I would like to engage mathematicians to plot a randomly acting
injury or adverse genetic property against the major to-and-fro cortico-cortical connections
and see how cortices situated in converging glutamatergic pathways fare in terms of vulnerability
risk. Based on my work, I presume vulnerability is determined by afferent signals of endangerment.
Such a model predicts the presence of signaling neurons (probably interneurons) which transmit the
injury signal and keep doing it despite the demise of large projection neurons. These neurons may be
cortical inhibitory interneurons that express neuronal NOS and are capable of releasing NO in their
environment when appropriately signaled. This hypothesis must be tested in subjects with early
disease. Drugs inhibiting this intrinsic signaling system should be considered.
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See above. I believe that neurodegeneration is development running amok,for
example uses developmentally powerful mechanisms (apoptosis) under "inappropriate"
conditions. The secret is why developmental signals (Pandora's box)are unleashed.
I suppose multiple initial subthreshold causes convene and trigger death, but there
must be a critical link in this cascade that might be a reasonable pharmacological
target. Given the overdetermined nature of developmental processes, this task will
not be easy. I believe that development holds the key. "Junk" neuropathologies
such as amyloid PHF and other famous accumulating misfolded proteins are likely
secondary to the global, over-regulated, cell demise |
See projects I would like to pursue. |
Not a very optimistic one. If this problem is not
neurodevelopment running amok, then it may be a coded time
in our genome -or elsewhere?- which dictates that the brain
cannot live more than a certain period. I suppose this may
be the case with a portion of age-associated neurodegeneration. |
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