Anne M. Cataldo, Ph.D.
Associate Professor
Departments of Psychiatry and Neuropathology
Harvard Medical School
(845)398-5426
cataldo@nki.rfmh.org

Dr. Cataldo is a Scientific Consultant at the Center for Dementia Research. She is also an Associate Professor of Psychiatry/Neuropathology at Harvard Medical School, and Director of the Laboratory of Molecular Neuropathology at McLean Hospital.

Education

Research Interests

My research projects focus on identifying and characterizing the cellular mechanisms underlying b-amyloidogenesis in sporadic and familial Alzheimer's disease and Down syndrome. The roles of the endocytic pathway and lysosomal system in APP processing leading to Ab generation have been central themes in these studies. Current investigations involve characterizing the normal functions of these trafficking systems in neurons of human brain, identifying abnormalities in these systems and their relationship to the neuropathology in AD, and generating new animal and cell models of the AD-relevant neuropathology.

Individual studies will: 1) seek evidence for altered APP processing and Ab production within the endocytic pathway and lysosomal system in human AD brain; 2) characterize a new in vivo model of early stage sporadic AD; 3) generate and characterize cell models of endocytic pathway and hydrolase trafficking abnormalities identified in human AD and their role in b-amyloidogenesis; 4) investigate the accentuation of endocytic-lysosomal system abnormalities by AD risk factors; 5) investigate the implications of endocytic pathway and lysosomal system abnormalities identified in the brain parenchyma on Ab clearance at the level of the cerebral endothelia; 6) study the role of cholesterol on the central vacuolar systems leading to alterations in APP processing/Ab generation.

Selected Publications

Grbovic, OM, Schmidt, SD, Mathews, PM, Nixon, RA, Cataldo, AM. (2002) Rab5 overexpression in a cell model of AD-related endocytic abnormalities influences processing of beta APP. Neurobiol. of aging. 23:50-3926.

Mathews, PM, Guerra, CB, Jiang, Y, Grbovic, OM, Kao, BH, Schmidt, SD, Dinakar, R, Mercken, M, Hille-Rehfeld, A, Rohrer, J, Mehta, P, Cataldo, AM, Nixon, RA. (2002) Alzheimer's disease-related overexpression of the cation- dependent mannose 6-phosphate receptor increases A beta secretion - Role for altered lysosomal hydrolase distribution in beta-amyloidogenesis. J Biol.Chem. 277:5299-5307.

Rao MV, Engle LJ, Mohan PS, Yuan A, Qiu D, Cataldo A, Hassinger L, Jacobsen S, Lee VM, Andreadis A, Julien JP, Bridgman PC, Nixon RA. (2002) Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density. J Cell Biol. 159:279-90.

Cataldo, A, Rebeck, GW, Ghetti, B, Hulette, C, Lippa, C, Van Broeckhovan, C, Van Duijn, C, Cras, P, Bogdanovic, N, Bird, T, Peterhoff, C, Nixon, R. (2001) Endocytic disturbances distinguish among subtypes of Alzheimer's disease and related disorders. Annals of Neurol. 50:661-665.

Mathews PM; Guerra CB; Jiang Y; Kao BH; Dinakar R; Mehta P; Cataldo AM; Nixon RA. (2001) Accelerated A-beta generation in a cell model of Alzheimer's disease-related endosomal-lysomal system upregulation. In: Alzheimer's disease: advances in etiology, pathogenesis and therapeutics / Iqbal K; Sisodia SS; Winblad B (eds) Chichester: Wiley. p. 461-467

Nixon RA, Mathews PM, Cataldo AM. (2001) The neuronal endosomal-lysosomal system in Alzheimer's disease. J. Alzheimer's Disease. 3:97-107.

Adamec E, Mohan PS, Cataldo AM, Vonsattel JP, Nixon RA. (2000) Up-regulation of the lysosomal system in experimental models of neuronal injury: implications for Alzheimer's disease. Neurosci. 100:663-75. 

Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA. (2000) Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Amer. J. Path. 157:277-86.

Mathews PM, Cataldo AM, Kao BH, Rudnicki AG, Qin X, Yang JL, Jiang Y, Picciano M, Hulette C, Lippa CF, Bird TD, Nochlin D, Walter J, Haass C, Levesque L, Fraser PE, Andreadis A, Nixon RA. (2000) Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease. Molec. Med. 6:878-91.

Nixon RA, Cataldo AM, Mathews PM. (2000) The endosomal-lysosomal system of neurons in Alzheimer's disease pathogenesis: a review. Neurochem. Res. 25:1161-72.

Shiurba RA, Spooner ET, Ishiguro K, Takahashi M, Yoshida R, Wheelock TR, Imahori K, Cataldo AM, Nixon RA. (1998) Immunocytochemistry of formalin-fixed human brain tissues: microwave irradiation of free-floating sections. Brain Res. Prot. 2:109-19. 

Troncoso JC, Cataldo AM, Nixon RA, Barnett JL, Lee MK, Checler F, Fowler DR, Smialek JE, Crain B, Martin LJ, Kawas CH. (1998) Neuropathology of preclinical and clinical late-onset Alzheimer's disease. Ann. Neurol. 43:673-6.

Cataldo AM, Barnett JL, Pieroni C, Nixon RA. (1997) Increased neuronal endocytosis and protease delivery to early endosomes in sporadic Alzheimer's disease: neuropathologic evidence for a mechanism of increased beta-amyloidogenesis. J. Neurosci. 17:6142-51.

Grynspan F, Griffin WR, Cataldo A, Katayama S, Nixon RA. (1997) Active site-directed antibodies identify calpain II as an early-appearing and pervasive component of neurofibrillary pathology in Alzheimer's disease. Brain Res. 763:145-58.