Neurobiology of Mild Cognitive Impairment in the Elderly
Program project funded by the National Institute on Aging (PO1 AG14449)

Dr. Elliott Mufson, Rush University Medical Center
Program Director

Photo courtesy of University of Kentucky

Advancement of our understanding of the relationship between the brain and memory problems in the elderly, as well as the design of effective treatments and therapies for brain diseases and disorders is a task requiring the scientific expertise and dedication of many researchers. Rush University Medical Center is the home of a major NIA funded research program project grant entitled “Neurobiology of mild cognitive impairment in the elderly,” directed by Dr. Elliott Mufson, Alla and Solomon Jesmer Chair in Aging, Professor of Neurological Sciences. This program project brings together the expertise of scientists in the areas of aging and dementia at Rush, with distinguished researchers located at other major academic research centers including:

Dr. Lester Binder, Northwestern University Medical School

Dr. Steven DeKosky, University of Pittsburgh Medical School

Dr. Dennis Dickson, Mayo Clinic, Jacksonville

Dr. Stephen Ginsberg, Nathan Kline Institute, NYU Medical Center

Dr. Allan Levey, Emory University

Dr. Stephen W. Scheff, University of Kentucky

Drs. John Trojanowski and Virginia T. Lee, University of Pennsylvania Medical School

The research program has an Administrative and Tissue Distribution Core (Director, Elliott Mufson) and a Statistical and Date Management Core (Director, Dr. Sue Leurgans). The program project works closely with the Rush Alzheimer’s Disease Center.

Program Project Publications

Ginsberg SD, Che S, Counts SE, Mufson EJ.  Single cell gene expression profiling in Alzheimer's disease.  NeuroRx. 2006 Jul;3(3):302-18

Counts SE, Nadeem M, Lad SP, Wuu J, Mufson EJ.  Differential expression of synaptic proteins in the frontal and temporal cortex of elderly subjects with mild cognitive impairment. J Neuropathol Exp Neurol. 2006 Jun;65(6):592-601

Dubelaar EJ, Mufson EJ, ter Meulen WG, Van Heerikhuize JJ, Verwer RW, Swaab DF.
Ginsberg SD, Che S, Wuu J, Counts SE, Mufson EJ.  Down regulation of trk but not p75NTR gene expression in single cholinergic basal forebrain neurons mark the progression of Alzheimer's disease. J Neurochem. 2006 Apr;97(2):475-87. Epub 2006 Mar 15

Ginsberg SD, Che S, Counts SE, Mufson EJ. Shift in the ratio of three-repeat tau and four-repeat tau mRNAs in individual cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer's disease. J Neurochem. 2006 Mar;96(5):1401-8

Counts SE, Chen EY, Che S, Ikonomovic MD, Wuu J, Ginsberg SD, Dekosky ST, Mufson EJ. Galanin fiber hypertrophy within the cholinergic nucleus basalis during the progression of Alzheimer's disease. Dement Geriatr Cogn Disord. 2006;21(4):205-14. Epub 2006 Jan 12

Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging. 2006 Oct;27(10):1372-84. Epub 2005 Nov 9

Ikonomovic MD, Mufson EJ, Wuu J, Cochran EJ, Bennett DA, DeKosky ST. Cholinergic plasticity in hippocampus of individuals with mild cognitive impairment: correlation with Alzheimer's neuropathology. J Alzheimers Dis. 2003 Feb;5(1):39-48

Mufson EJ, Counts SE, Ginsberg SD. Gene expression profiles of cholinergic nucleus basalis neurons in Alzheimer's disease. Neurochem Res. 2002 Oct;27(10):1035-48

Mitchell TW, Mufson EJ, Schneider JA, Cochran EJ, Nissanov J, Han LY, Bienias JL, Lee VM, Trojanowski JQ, Bennett DA, Arnold SE. Parahippocampal tau pathology in healthy aging, mild cognitive impairment, and early Alzheimer's disease. Ann Neurol. 2002 Feb;51(2):182-9

DeKosky ST, Ikonomovic MD, Styren SD, Beckett L, Wisniewski S, Bennett DA, Cochran EJ, Kordower JH, Mufson EJ. Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment. Ann Neurol. 2002 Feb;51(2):145-55

Mufson EJ, Ma SY, Dills J, Cochran EJ, Leurgans S, Wuu J, Bennett DA, Jaffar S, Gilmor ML, Levey AI, Kordower JH. Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease. J Comp Neurol. 2002 Feb 4;443(2):136-53

Mitchell TW, Nissanov J, Han LY, Mufson EJ, Schneider JA, Cochran EJ, Bennett DA, Lee VM, Trojanowski JQ, Arnold SE. Novel method to quantify neuropil threads in brains from elders with or without cognitive impairment. J Histochem Cytochem. 2000 Dec;48(12):1627-38

DeKosky ST, Marek K. Looking backward to move forward: early detection of neurodegenerative disorders. Science. 2003 Oct 31;302(5646):830-4.

Bodner SM, Berrettini W, van Deerlin V, Bennett DA, Wilson RS, Trojanowski JQ, Arnold SE. Genetic variation in the brain derived neurotrophic factor gene in Alzheimer's disease. Am J Med Genet B Neuropsychiatr Genet. 2005 Apr 5;134(1):1-5

Grossman M, Farmer J, Leight S, Work M, Moore P, Van Deerlin V, Pratico D, Clark CM, Coslett HB, Chatterjee A, Gee J, Trojanowski JQ, Lee VM. Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease. Ann Neurol. 2005 May;57(5):721-9.

de Leon MJ, DeSanti S, Zinkowski R, Mehta PD, Pratico D, Segal S, Rusinek H, Li J, Tsui W, Saint Louis LA, Clark CM, Tarshish C, Li Y, Lair L, Javier E, Rich K, Lesbre P, Mosconi L, Reisberg B, Sadowski M, DeBernadis JF, Kerkman DJ, Hampel H, Wahlund LO, Davies P. Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment. Neurobiol Aging. 2006 Mar;27(3):394-401. Epub 2005 Aug 26

Trojanowski JQ, Lee VM. Pathological tau: a loss of normal function or a gain in toxicity?
Nat Neurosci. 2005 Sep;8(9):1136-7

Andersen OM, Reiche J, Schmidt V, Gotthardt M, Spoelgen R, Behlke J, von Arnim CA, Breiderhoff T, Jansen P, Wu X, Bales KR, Cappai R, Masters CL, Gliemann J, Mufson EJ, Hyman BT, Paul SM, Nykjaer A, Willnow TE.  Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein.Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13461-6. Epub 2005 Sep 7

Peng S, Wuu J, Mufson EJ, Fahnestock M.Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer's disease. JNeurochem. 2005 Jun;93(6):1412-21

Counts SE, Chen EY, Ginsberg SD, Kordower JH, Mufson EJ. RNA amplification of bromodeoxyuridine labeled newborn neurons in the monkey hippocampus. J Neurosci Methods. 2005 Jun 15;144(2):197-201. Epub 2004 Dec 21

Mufson EJ, Counts SE, Perez SE, Binder L. Galanin plasticity in the cholinergic basal forebrain in Alzheimer's disease and transgenic mice. Neuropeptides. 2005 Jun;39(3):233-7. Epub 2005 Feb 1

Counts SE, Mufson EJ. The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease. J Neuropathol Exp Neurol. 2005 Apr;64(4):263-72

Ikonomovic MD, Mufson EJ, Wuu J, Bennett DA, DeKosky ST. Reduction of choline acetyltransferase activity in primary visual cortex in mild to moderate Alzheimer's disease. Arch Neurol. 2005 Mar;62(3):425-30

Georganopoulou DG, Chang L, Nam JM, Thaxton CS, Mufson EJ, Klein WL, Mirkin CA. Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease. Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2273-6. Epub 2005 Feb 4

Counts SE, Nadeem M, Wuu J, Ginsberg SD, Saragovi HU, Mufson EJ. Reduction of cortical TrkA but not p75(NTR) protein in early-stage Alzheimer's disease. Ann Neurol. 2004 Oct;56(4):520-31
Peng S, Wuu J, Mufson EJ, Fahnestock M. Increased proNGF levels in subjects with mild cognitive impairment and mild Alzheimer disease. J Neuropathol Exp Neurol. 2004 Jun;63(6):641-9.

Ginsberg SD, Elarova I, Ruben M, Tan F, Counts SE, Eberwine JH, Trojanowski JQ, Hemby SE, Mufson EJ, Che S. Single-cell gene expression analysis: implications for neurodegenerative and neuropsychiatric disorders. Neurochem Res. 2004 Jun;29(6):1053-64

Wang DS, Bennett DA, Mufson E, Cochran E, Dickson DW.  Decreases in soluble alpha-synuclein in frontal cortex correlate with cognitive decline in the elderly. Neurosci Lett. 2004 Apr 8;359(1-2):104-8

Mufson EJ, Ginsberg SD, Ikonomovic MD, DeKosky ST. Human cholinergic basal forebrain: chemoanatomy and neurologic dysfunction. J Chem Neuroanat. 2003 Dec;26(4):233-42

Wang DS, Bennett DA, Mufson EJ, Mattila P, Cochran E, Dickson DW.  Contribution of changes in ubiquitin and myelin basic protein to age-related cognitive decline. Neurosci Res. 2004 Jan;48(1):93-100

Lad SP, Neet KE, Mufson EJ.  Nerve growth factor: structure, function and therapeutic implications for Alzheimer's disease. Curr Drug Targets CNS Neurol Disord. 2003 Oct;2(5):315-34

Mufson EJ, Ikonomovic MD, Styren SD, Counts SE, Wuu J, Leurgans S, Bennett DA, Cochran EJ, DeKosky ST.  Preservation of brain nerve growth factor in mild cognitive impairment and Alzheimer disease. Arch Neurol. 2003 Aug;60(8):1143-8.

Kus L, Borys E, Ping Chu Y, Ferguson SM, Blakely RD, Emborg ME, Kordower JH, Levey AI, Mufson EJ. Distribution of high affinity choline transporter immunoreactivity in the primate central nervous system. J Comp Neurol. 2003 Aug 25;463(3):341-57

Yang Y, Mufson EJ, Herrup K. Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease. J Neurosci. 2003 Apr 1;23(7):2557-63

Yao Y, Clark CM, Trojanowski JQ, Lee VM, Pratico D. Elevation of 12/15 lipoxygenase products in AD and mild cognitive impairment. Ann Neurol. 2005 Oct;58(4):623-6.

Trojanowski JQ, Lee VM. Rous-Whipple Award Lecture. The Alzheimer's brain: finding out what's broken tells us how to fix it. Am J Pathol. 2005 Nov;167(5):1183-8