www.andropause.org.uk

back to Programme

ANDROGENS AND BRAIN FUNCTION

Prof. Suzana Petanceska,

NYU School of Medicine and the Nathan Kline Institute,

New York, USA.

Alzheimer's disease (AD) is characterized by the intracranial accumulation of the 4 kDa amyloid beta peptide (A beta), following proteolysis of a approximately 700 amino acid, integral membrane precursor, the amyloid beta precursor protein (APP).

The best evidence causally linking APP to AD has been provided by the discovery of mutations within the APP coding sequence that segregate with disease phenotypes in autosomal dominant forms of familial AD (FAD). Though FAD is rare (< 10% of all AD), the hallmark features--amyloid plaques, neurofibrillary tangles, synaptic and neuronal loss, neurotransmitter deficits, dementia--are indistinguishable when FAD is compared with typical, common, 'non-familial', or sporadic AD (SAD).

Studies of some clinically relevant mutant APP molecules from FAD families have yielded evidence that APP mutations can lead to enhanced generation or aggregability of A beta, consistent with a pathogenic role in AD. Other genetic loci for FAD have been discovered which are distinct from the immediate regulatory and coding regions of the APP gene, indicating that defects in molecules other than APP can also specify cerebral amyloidogenesis and FAD. To date, all APP and non-APP FAD mutations can be demonstrated to have the common feature of promoting amyloidogenesis of A beta.

Epidemiological studies indicate that postmenopausal women on oestrogen hormone replacement therapy (HRT) have their relative risk of developing SAD diminished by about one-third as compared with age- matched women not receiving HRT. Because of the key role of cerebral A beta accumulation in initiating AD pathology, it is most attractive that oestradiol might modulate SAD risk or age-at-onset by inhibiting A beta accumulation. A possible mechanistic basis for such a scenario is reviewed here.

 Professor Suzana S. Petanceska, BSc, PhD.

Assistant Professor of Psychiatry and Cell Biology

NYU School of Medicine and the Nathan Kline Institute,

New York, USA.

Email: Petances@NKI.RFMH.ORG

Education:

1990       B.Sc.             University of Belgrade, Yugoslavia (Molecular Biology and Physiology)

1995      Ph.D.             Sackler Institute for Graduate Biomedical Studies, NYU Graduate School of Arts and Sciences (Pharmacology)

Postdoctoral Training:

            4/95-2/98                 Postdoctoral Associate,

                                            Laboratory for Molecular and Cellular Neuroscience

                                            Rockefeller University

            3/98-5/01                  Postdoctoral Fellow

                                            Center for Dementia Research, Nathan Kline Institute

Academic Appointments:

           6/01-present             Assistant Professor, Department of Psychiatry

                                             NYU Medical Center

Recent Publications:

            1.             Petanceska SS, DeRosa S, Olm V, Diaz N, Sharma A, Thomas-Bryant T et al. Statin therapy for Alzheimer's disease: will it work? J Mol.Neurosci. 2002;19:155-61.

            2.             Pappolla MA, Smith MA, Bryant-Thomas T, Bazan N, Petanceska S, Perry G et al. Cholesterol, oxidative stress, and Alzheimer's disease: expanding the horizons of pathogenesis. Free Radic.Biol.Med. 2002;173-81.

            3.             Gandy S,.Petanceska S. Regulation of alzheimer beta-amyloid precursor trafficking and metabolism. Adv.Exp.Med.Biol. 2001;487:85-100.

            4.             Petanceska SS, Nagy V, Frail D, Gandy S. Ovariectomy and 17beta-estradiol modulate the levels of Alzheimer's amyloid beta peptides in brain. Exp.Gerontol. 2000;35:1317-25.

            5.             Gandy S,.Petanceska S. Regulation of Alzheimer beta-amyloid precursor trafficking and metabolism. Biochim.Biophys.Acta 2000;1502:44-52.

            6.             Petanceska SS, Seeger M, Checler F, Gandy S. Mutant presenilin 1 increases the levels of Alzheimer amyloid beta- peptide Abeta42 in late compartments of the constitutive secretory pathway. J Neurochem. 2000;74:1878-84.