Carmela Abraham, PhD

Professor of Biochemistry and Medicine

abrahamcolor1_001Dr. Carmela Abraham completed her undergraduate degree at Tel Aviv University, Israel. She earned her PhD degree in Neurobiology from Harvard University. She joined the Boston University School of Medicine’s Departments of Medicine and Biochemistry in 1989 as an Assistant Professor and has since been promoted to Professor.

Research Interests

Dr. Abraham’s research interests are focused on the etiology of Alzheimer’s disease and the role of the Amyloid Precursor Protein (APP) and Abeta peptide in the development of the disease, as well as identifying molecular mechanisms leading to normal brain aging and the pathological processes that culminate in Alzheimer’s disease and multiple sclerosis. She also studies enzymes that break down the toxic Abeta peptide as a means to therapeutically clear the brain of this peptide. Genetic and molecular studies indicate that Abeta initiates the neurodegenerative aspects of Alzheimer’s disease. Dr. Abraham has also identified genes that play crucial roles in brain dysfunction leading to cognitive decline. Specifically, Dr. Abraham is studying Klotho, a cytoprotective, anti- aging protein. She is working on identifying Klotho receptors in the brain and to define the signaling pathways by which Klotho exerts its protective effects on neurons and oligodendrocytes. She is also studying Klotho’s transcriptional regulation and has identified compounds to therapeutically exploit these protective effects.

ADC Role

Basic scientist collaborating with ADC scientists.

Awards/Memberships

Dr. Abraham is the recipient of The Neuroscience Education and Research Foundation Award for an Outstanding Promise as a Young Alzheimer Investigator (1990). Moreover she is the recipient of the highest awards from the Alzheimer’s Association – The Zenith Award (1994) and the Temple Award (1999). She is a member of the Society for Neuroscience, American Society for Neurochemistry, American Association of Neuropathologists, New York Academy of Science, International Society for Amyloidosis, American Academy for the Advancement of Science, among others.

Recent Publications

Mehi SJ, Maltare A, Abraham CR, King GD. MicroRNA-339 and microRNA-556 regulate Klotho expression in vitro. Age (Dordr). 2014 Feb; 36(1): 141-49 PDF

So PP, Khodr CE, Chen CD, Abraham CR. Comparable dimerization found in wildtype and familial Alzheimer’s disease amyloid precursor protein mutants. Am J Neurodegener Dis. 2013; 2(1): 15-28. [PDF]

Chen CD, Sloane JA, Li H, Aytan N, Giannaris EL, Zeldich E, Hinman JD, Dedeoglu A, Rosene DL, Bansal R, Luebke JI, Kuro-o M, Abraham CR. The antiaging protein Klotho enhances oligodendrocyte maturation and myelination of the CNS. J Neurosci. 2013 Jan 30;33(5):1927-39. doi: 10.1523/JNEUROSCI.2080-12.2013.

McKee AC, Stein TD, Nowinski CJ, Stern RA, Daneshvar DH, Alvarez VE, Lee HS, Hall G, Wojtowicz SM, Baugh CM, Riley DO, Kubilus CA, Cormier KA, Jacobs MA, Martin BR, Abraham CR, Ikezu T, Reichard RR, Wolozin BL, Budson AE, Goldstein LE, Kowall NW, Cantu RC. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013 Jan;136(Pt 1):43-64. doi: 10.1093/brain/aws307. Epub 2012 Dec

Abraham CR, Chen C, Cuny GD, Glicksman MA, Zeldich E. Small-molecule Klotho enhancers as novel treatment of neurodegeneration. Future Med Chem. 2012 Sep;4(13):1671-9. doi: 10.4155/fmc.12.134.

So PP, Zeldich E, Seyb KI, Huang MM, Concannon JB, King GD, Chen CD, Cuny GD, Glicksman MA, Abraham CR. Lowering of amyloid beta peptide production with a small molecule inhibitor of amyloid-β precursor protein dimerization. Am J Neurodegener Dis. 2012 May 30;1(1):75-87.

King GD, Huang MM, Schuman ER, Chen CD, Cuny GD, Glicksman MA, Abraham CR. (2012) Identification of novel small molecules to modulate transcription of Klotho. Biochem. J. 441:453-61.

Abraham CR and Nagle MW (2011) Acylaminoacyl-peptidase in Handbook of Proteolytic Enzymes, 3rd Edition.

Abraham CR (2011) Amyloid beta peptide and the Amyloid cascade hypothesis. In The Handbook of Alzheimer’s Disease and Other Dementias, First Edition. Edited by Andrew E. Budson, Neil W. Kowall. Published by Blackwell Publishing Ltd.

King GD, Rosene DL, Abraham CR (2011) Promoter methylation and age-related downregulation of klotho in rhesus monkey. AGE, Sept. 16. Epub.

So P, Chen CD, Abraham CR (2011) Detection of Wild Type and Mutant Amyloid Precursor Protein Dimerization Using Beta-Galactosidase Enzyme Fragment Complementation. J. Alz Dis. 26:647-55.

Porat ME, Lunetta KL, Cupples LA, Abraham CR, Green RC, Baldwin CT, Farrer LA (2010) Serum paraoxonase activity is associated with variants in the PON gene cluster and risk of Alzheimer disease. Neurobiol. Aging. Oct. 25.

Oh SY, Chen CD, Abraham CR (2010) Cell-type Dependent Modulation of Notch Signaling by the Amyloid Precursor Protein. J. Neurochem. 113:262-74.

Zhao YR, O’Connor PB, McKee AC, Abraham CR. (2009) Acyl Peptide Hydrolase Degrades Monomeric and Oligomeric Amyloid-Beta Peptide. Molecular Neurodegeneration. 4:33.

Cordy JM, Zerbinatti CV, Chen CD, Guillily M, Suon S, Ray WJ, Seabrook GR, Abraham CR, Wolozin B. (2008) Oxysterol-binding protein-1 (OSBP-1) modulates processing and trafficking of the amyloid precursor protein. Molecular Neurodgeneration. 3:5.

Hinman JD, Oh SY, Chen CD, Hollander W, Abraham CR. (2008) Age-dependent accumulation of ubiquitinated CNP in myelin lipid rafts. Glia. 56:118-33.

Duce JA, Podvin S, Hollander W, Kipling D, Rosene DL, Abraham CR. (2008) Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey. Glia. 56:106-17.

Chen CD, Podvin S, Gillespie E, Leeman S, Abraham CR. (2007) Insulin Stimulates the Cleavage and Release of the Extracellular Domain of Klotho via ADAM10 and ADAM17, PNAS. 104:19796-19801.

Hinman JD and Abraham CR (2007) What’s behind the decline? – The role of white matter in brain aging. Neurochem. Res. 32:2023-31.

Yamin R, Bagchi S, Hildebrant R, Scaloni A, Widom RL, Abraham CR. (2007) Acyl Peptide Hydrolase, a serine proteinase isolated from conditioned medium of neuroblastoma cells, degrades the amyloid ß peptide. J. Neurochem. 100:458-467.

Chen CD, Oh SY, Hinman JD, Abraham CR. (2006) Visualization of APP dimerization and APP-Notch heterodimerization in living cells using bimolecular fluorescence complementation. J. Neurochem, 97:30-43.

Duce JA, Hollander W, Jaffe R, Abraham CR. (2006) Early complement activation targets myelin and oligodendrocytes in the aged rhesus monkey brain. Neurobiol Aging. 27:633-644.

Oh SY, Ellenstein A, Chen CD, Hinman JD, Berg EA, Costello CE, Yamin R, Neve RL, Abraham CR (2005) The Amyloid Precursor Protein interacts with Notch receptors. J. Neurosci. Res. 82:32-42.

Hinman JD, Peters A, Rosene DL, Hollander W, Rasband M, Abraham CR. (2005) Age-related molecular reorganization at the node of Ranvier. J. Comp. Neurol. 495:351-362.

Hinman JD, Duce JA, Siman R, Hollander W, Abraham CR (2004) Activation of calpain-1 in myelin and microglia in the white matter of the aged rhesus monkey. J. Neurochem. 89:430-441.