Publications (87)315.73 Total impact
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Article: Familial Cerebral Amyloid Angiopathies and Dementia
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ABSTRACT: Amyloidosis is a disorder of protein conformation leading to aggregation. The term defines a diverse group of proteins normally present in body fluids as soluble precursors that can be deposited as insoluble amyloid fibrils in different tissues producing organ dysfunction and cell death. These fibrils are composed of self-assembled, low molecular weight mass peptides adopting β-pleated sheet structure, the conformation responsible for their physicochemical properties and tinctoreal characteristics. So far, 20 different proteins have been identified as subunits of amyloid fibrils (Westermark et al., 1999). Collectively, they are products of normal genes; however, several amyloid precursors contain abnormal amino acid substitutions that can impose an unusual potential for self-aggregation. The molecular mass of the amyloid peptides is within the 4 to 30-kDa range, with heterogeneity at the amino-and carboxyl-terminal portions found in most amyloid proteins. Increased levels of amyloid precursors, either in the circulation or locally in sites of deposition, are usually the result of overexpression or defective clearance, or both. Of the 20 amyloid proteins identified, few of them are known to cause amyloid deposition in the central nervous system, which in turn results in cognitive deficits, dementia, stroke, cerebellar and extrapyramidal signs, or a combination of them.Alzheimer Disease and Associated Disorders 07/2012; 14(1):S25-S30. · 2.81 Impact Factor -
Chapter: Inherited Amyloidoses and Neurodegeneration: Familial British Dementia and Familial Danish Dementia
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ABSTRACT: Distinct mutations of the BRI2 gene are associated with two hereditary neurodegenerative diseases with striking resemblance to Alzheimer's disease. In both familial British dementia and familial Danish dementia, there are widespread cerebral parenchymal amyloid and preamyloid plaques, severe cerebral amyloid angiopathy and neurofibrillary tangle pathology. Both diseases are associated with distinct mutations of the BRI2 gene, resulting in generation of extended BRI2 precursor proteins and the release of two de novo created amyloidogenic peptides: ABri in familial British dementia and ADan in familial Danish dementia. Similar to Aβ peptide, the ABri and ADan amyloid subunits are neurotoxic; they can elicit a marked astrocytic and activated microglial response and are able to activate both the classic and alternative complement pathways. In addition, synthetic ABri and ADan oligomers are able to trigger apoptotic pathways and form ion channel-like structures in vitro. The data provided by research into these rare hereditary cerebral amyloid diseases reaffirm the notion that non-Aβ amyloidosis may provide an opportunity for studying the role of cerebral amyloid deposition in the mechanism of neurodegeneration.09/2011: pages 439 - 445; , ISBN: 9781444341256 -
Article: Greater risk of Alzheimer's disease in older adults with insomnia.
Journal of the American Geriatrics Society 03/2011; 59(3):559-62. · 3.74 Impact Factor -
Article: PYROGLUTAMATE FORMATION AT THE N-TERMINI OF ABRI MOLECULES IN FAMILIAL BRITISH DEMENTIA IS NOT RESTRICTED TO THE CENTRAL NERVOUS SYSTEM.
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ABSTRACT: Amyloid molecules harboring pyroglutamate (pGlu) residue at the N-termini are considered to be important for the development of cerebral amyloidosis such as Alzheimer's disease and thought to be either spontaneously generated or being catalyzed by glutaminyl cyclase. Familial British dementia (FBD) is an autosomal dominant form of dementia neuropathologically characterized by parenchymal amyloid and preamyloid deposits, extensive cerebral amyloid angiopathy, and neurofibrillary tangles. FBD is caused by a stop to Arg mutation in the BRI2 gene, generating de novo created amyloid molecule ABri which accumulates in FBD brains but is not present in the normal population. Soluble ABri molecules present in the circulation of carriers of the BRI2 mutation are 34 amino acids long exclusively harboring Glu residue at the N-termini (ABri1-34E), whereas water- and formic acid-soluble ABri molecules extracted from FBD brains have abundant ABri species bearing pGlu residue (ABri1-34pE), suggesting that pyroglutamate formation occurs at the site of deposition. In order to further clarify the mechanism (s) of ABri deposition, we studied whether pyroglutamate formation indeed occurs outside the central nervous system taking advantage that FBD is also a systemic amyloidosis. Soluble and fibrillar ABri molecules extracted from systemic organs and analyzed biochemically using a combination of immunoprecipitation, mass spectrometry, and western blot analysis were oligomeric in size and contained a large proportion of ABri1-34pE. The data indicate that pyroglutamate formation at the N-termini of ABri molecules is an early step in the process of FBD amyloid deposition, and its formation is not restricted to the central nervous system.Hirosaki Medical Journal 07/2010; 61(Suppl):S262-S269. -
Article: CEREBRAL AMYLOID ANGIOPATHY AND ALZHEIMER'S DISEASE.
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ABSTRACT: Cerebral amyloid angiopathy (CAA) is increasingly recognized as a major contributor of Alzheimer's disease (AD) pathogenesis. To date, vascular deposits and not parenchymal plaques appear more sensitive predictors of dementia. Amyloid deposition in and around cerebral blood vessels plays a central role in a series of response mechanisms that lead to changes in the integrity of the blood-brain barrier, extravasations of plasma proteins, edema formation, release of inflammatory mediators and matrix metalloproteases which, in turn, produce partial degradation of the basal lamina with the potential to develop hemorrhagic complications. The progressive buildup of amyloid deposits in and around blood vessels chronically limits blood supply and causes focal deprivation of oxygen, triggering a secondary cascade of metabolic events several of which involve the generation of nitrogen and oxygen free radicals with consequent oxidative stress and cell toxicity. Many aspects of CAA in early- and late-onset AD -the special preference of Aβ40 to deposit in the vessel walls, the favored vascular compromise associated with many Aβ genetic variants, the puzzling observation that some of these vasculotropic variants solely manifest with recurrent hemorrhagic episodes while others are mainly associated with dementia- await clarification. Non-Aβ cerebral amyloidoses reinforce the viewpoint that plaque burden is not indicative of dementia while highlighting the relevance of nonfibrillar lesions and vascular involvement in the disease pathogenesis. The lessons learned from the comparative study of Aβ and non-Aβ cerebral amyloidosis provide new avenues and alternative models to study the role of amyloid in the molecular basis of neurodegeneration.Hirosaki Medical Journal 07/2010; 61(Suppl):S111-S124. -
Article: Iowa variant of familial Alzheimer's disease: accumulation of posttranslationally modified AbetaD23N in parenchymal and cerebrovascular amyloid deposits.
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ABSTRACT: Mutations within the amyloid-beta (Abeta) sequence, especially those clustered at residues 21-23, which are linked to early onset familial Alzheimer's disease (AD), are primarily associated with cerebral amyloid angiopathy (CAA). The basis for this predominant vascular amyloid burden and the differential clinical phenotypes of cerebral hemorrhage/stroke in some patients and dementia in others remain unknown. The AbetaD23N Iowa mutation is associated with progressive AD-like dementia, often without clinically manifested intracerebral hemorrhage. Neuropathologically, the disease is characterized by predominant preamyloid deposits, severe CAA, and abundant neurofibrillary tangles in the presence of remarkably few mature plaques. Biochemical analyses using a combination of immunoprecipitation, mass spectrometry, amino acid sequence, and Western blot analysis performed after sequential tissue extractions to separately isolate soluble components, preamyloid, and fibrillar amyloid species indicated that the Iowa deposits are complex mixtures of mutated and nonmutated Abeta molecules. These molecules exhibited various degrees of solubility, were highly heterogeneous at both the N- and C-termini, and showed partial aspartate isomerization at positions 1, 7, and 23. This collection of Abeta species-the Iowa brain Abeta peptidome-contained clear imprints of amyloid clearance mechanisms yet highlighted the unique neuropathological features shared by a non-Abeta cerebral amyloidosis, familial Danish dementia, in which neurofibrillary tangles coexist with extensive pre-amyloid deposition in the virtual absence of fibrillar lesions. These data therefore challenge the importance of neuritic plaques as the sole contributors for the development of dementia.American Journal Of Pathology 03/2010; 176(4):1841-54. · 4.89 Impact Factor -
Article: Diminished amyloid-beta burden in Tg2576 mice following a prophylactic oral immunization with a salmonella-based amyloid-beta derivative vaccine.
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ABSTRACT: Immunotherapy holds great promise for Alzheimer's disease (AD) and other conformational disorders but certain adverse reactions need to be overcome. Prior to the side effects in the first Elan/Wyeth AD vaccine trial, we proposed using amyloid-beta (Abeta) derivatives as a safer approach. The route of administration may also affect vaccine safety. To assess the feasibility of oral immunization that promotes mucosal immunity, Tg2576 AD model mice were treated prophylactically three times over 6 weeks starting at 3-5 months of age with a Salmonella vaccine expressing K6Abeta(1-30). At 22-24 months of age, cortical Abeta plaque burden and total Abeta(40/42) levels were reduced by 48-75% in the immunized mice compared to controls, which received unmodified Salmonella. Plaque clearance was not associated with increased microglial activation, which may be explained by the long treatment period. Furthermore, cerebral microhemorrhages were not increased in the treated mice in contrast to several passive Abeta antibody studies. These results further support our findings with this immunogen delivered subcutaneously and demonstrate its efficacy when given orally, which may provide added benefits for human use.Journal of Alzheimer's disease: JAD 09/2009; 18(4):961-72. · 3.74 Impact Factor -
Article: C for T substitution at codon 108: the first identified silent mutation in the transthyretin gene
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ABSTRACT: Transthyretin (TTR) is a 55kDa tetrameric protein synthesized by the liver and the choroid plexus that binds thyroxine and retinol-binding protein. More than fifty mutations have been identified in the TTR gene, the majority of them associated with hereditary amyloidosis1. This study reveals the first silent mutation on the TTR gene : Ala108.07/2009; 4(1):52-53. -
Article: Genetics and molecular pathogenesis of sporadic and hereditary cerebral amyloid angiopathies.
Acta Neuropathologica 07/2009; · 9.32 Impact Factor -
Article: Antibody response and plasma Abeta1-40 levels in young Microcebus murinus primates immunized with Abeta1-42 and its derivatives.
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ABSTRACT: We have been developing Abeta derivative vaccines with the objective to improve the safety of Abeta targeting immunotherapy. Our Abeta homologs are designed to have less direct toxicity and to produce a modified immune response compared to Abeta. In extensive mouse studies, all our vaccines have improved cognition in transgenic mice while eliciting different immune responses and reducing brain amyloid burden to a variable degree. While we are continuing to characterize these vaccines in mice, in preparation for studies in old primates and for human trials we assessed their effect in young lemur primates (n=25) that with age develop Abeta plaques and tau aggregates as seen in Alzheimer's disease. In the primates, all the peptides administered with alum adjuvant elicited a moderate to robust anti-Abeta IgM response. Abeta1-42, K6Abeta1-30 and K6Abeta1-30[E(18)E(19)] resulted in a high anti-Abeta IgG response, whereas Abeta1-30[E(18)E(19)] produced a weaker more variable IgG titer. Notably, 22 weeks after the 3rd immunization, IgM and IgG levels in derivative-vaccinated primates were similar to preimmune values whereas Abeta1-42 treated primates maintained a moderate IgG titer. The increase in antibodies that recognized Abeta1-40 often correlated with increase in Abeta1-40 in plasma, which suggests that the antibodies were binding to Abeta in vivo. Interestingly, significant transient weight gain was observed (K6Abeta1-30-, Abeta1-30[E(18)E(19)]- and Abeta1-42-treated) or a trend in the same direction (K6Abeta1-30[E(18)E(19)]-treated, adjuvant controls) following the injections. Based on these findings, we have chosen K6Abeta1-30 for immunizations in old primates as the antibody response to this vaccine was less variable compared to other Abeta derivatives. Our present findings indicate that most of our Abeta derivatives elicit a substantial antibody response in primates, and importantly this effect is reversible which enhances the safety profile of our approach.Vaccine 01/2009; 27(7):957-64. · 3.77 Impact Factor -
Chapter: Conformation as Therapeutic Target in the Prionoses and Other Neurodegenerative Conditions
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ABSTRACT: Neurodegenerative conditions are increasing in prevalence as the average human life expectancy rises. Alzheimer’s disease (AD) is the fourth commonest cause of death in the United States; the recent outbreak of new variant Creutzfeldt-Jakob disease (nvCJD) has raised the specter of a large population being at risk to develop this prionosis. The pathogenesis of many neurodegenerative diseases is now recognized to be associated with abnormalities of protein conformation. A common theme in these disorders is the conversion of a soluble normal precursor protein into an insoluble, aggregated, ?-sheet rich form that is toxic. In AD, a critical event is the conversion of the normal, soluble A? (sA?) peptide into fibrillar A?, within neuritic plaques and congophilic angiopathy (1). Similarly, in the prionoses, the central event is the conversion of the normal prion protein, PrPC, to PrPSc (2). An increased ?-sheet content characterizes both A? and PrPSc.02/2008: pages 223-236; -
Chapter: Familial British and Danish Dementias
01/2008: pages 515 - 526; , ISBN: 9783527619344 -
Chapter: Apolipoprotein E and Amyloidogenesis
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ABSTRACT: Alzheimer's amyloid β-protein (Aβ) is a modified, pathogenic form of a constitutive host protein, soluble amyloid β-protein (SAβ). Both are conformational isomers encoded by the gene for the β-amyloid precursor protein (APP), located on chromosome 21. sAβ and Aβ have identical sequence but are thought to differ in their secondary structure and physicochemical properties, hence they are conformational isomers. sAβ is easily degraded, while Aβ is partially resistant. Aβ has a high β-pleated sheet content, while sAβ is thought to be more random-coil and/or α-helical. Aβ, unlike sAβ, adopts an amyloidogenic conformation, forms aggregates and gives rise to fibrils. Most early-onset forms of Alzheimer's disease (AD) have been linked to mutations of the presenilin 1, presenilin 2 or APP genes, located on chromosomes 14, 1 and 21, respectively. Their relationship to amyloidogenesis is being investigated. On the other hand, the major risk factor for the most common form, sporadic and familial late-onset AD, is the presence of the apoE ε4 allele. Recent studies have shown that a 10 kDa C-terminal fragment of apoE is complexed to Aβ in neuritic plaques and that apoE isoforms can modulate amyloid formation in vitro. Moreover, thrombin cleavage of apoE generates a similar C-terminal fragment that can form amyloid-like fibrils. Thus neuritic plaques may contain both Aβ and apoE amyloid fibrils. AD can be neuropathologically defined by the presence of several interacting proteins that can adopt an amyloidogenic conformation. This has led us to hypothesize that in AD, amyloidosis may be reactive rather than causative.09/2007: pages 132 - 145; , ISBN: 9780470514924 -
Article: Preferential association of serum amyloid P component with fibrillar deposits in familial British and Danish dementias: similarities with Alzheimer's disease.
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ABSTRACT: Two hereditary forms of cerebrovascular amyloidosis, familial British and Danish dementias (FBD and FDD), share striking similarities with Alzheimer's disease (AD) despite structural differences among their amyloid subunits (ABri in FBD, ADan in FDD, and Abeta in AD). Neuropathological lesions in these disorders include neurofibrillary tangles, parenchymal amyloid and pre-amyloid deposits and overwhelming cerebral amyloid angiopathy co-localizing with reactive microglia and multiple amyloid associated proteins including activation products of the complement cascade. Immunohistochemical analysis of FBD and FDD brain lesions unveiled the presence of serum amyloid P-component (SAP) primarily associated with thioflavin positive amyloid deposits in spite of the significant pre-amyloid burden existing in both disorders. Using affinity chromatography and ELISA binding assays we demonstrated specific, calcium-dependent, saturable, high affinity binding interactions between SAP and ABri/ADan peptides, with dissociation constant values in the sub-nanomolar range and within the same order of magnitude as those resulting from the interaction of SAP with Alzheimer's Abeta1-40 and Abeta1-42. The preferential association of SAP with fibrillar amyloid lesions and not with non-fibrillar pre-amyloid deposits is puzzling, suggesting that SAP modulates the assembly and stability of the final fibril rather than participating in the early steps of protein misfolding and oligomerization.Journal of the Neurological Sciences 07/2007; 257(1-2):88-96. · 2.35 Impact Factor -
Article: Novel prion protein conformation and glycotype in Creutzfeldt-Jakob disease.
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ABSTRACT: To describe a novel molecular and pathological phenotype of Creutzfeldt-Jakob disease. Patient A 69-year-old woman with behavioral and personality changes followed by rapidly evolving dementia. Postmortem examination of the brain showed intracellular prion protein deposition and axonal swellings filled with amyloid fibrils. Biochemical analysis of the pathological prion protein disclosed a previously unrecognized PrP(Sc) tertiary structure lacking diglycosylated species. Genetic analysis revealed a wild-type prion protein gene. The prion agent responsible for this atypical phenotype was successfully passaged to bank voles. To our knowledge, our results define a new human prion disorder characterized by intracellular accumulation of a novel type of pathological prion protein.Archives of Neurology 05/2007; 64(4):595-9. · 7.58 Impact Factor -
Article: Vaccination of Alzheimer's model mice with Abeta derivative in alum adjuvant reduces Abeta burden without microhemorrhages.
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ABSTRACT: Immunotherapy holds great promise for Alzheimer's disease (AD) and other conformational disorders but certain adverse reactions need to be overcome. The meningoencephalitis observed in the first AD vaccination trial was likely related to excessive cell-mediated immunity caused by the immunogen, amyloid-beta (Abeta) 1-42, and the adjuvant, QS-21. To avoid this toxicity, we have been using Abeta derivatives in alum adjuvant that promotes humoral immunity. Other potential side effects of immunotherapy are increased vascular amyloid and associated microhemorrhages that may be related to rapid clearance of parenchymal amyloid. Here, we determined if our immunization strategy was associated with this form of toxicity, and if the therapeutic effect was age-dependent. Tg2576 mice and wild-type littermates were immunized from 11 or 19 months and their behaviour evaluated prior to killing at 24 months. Subsequently, plaque- and vascular-Abeta burden, Abeta levels and associated pathology was assessed. The therapy started at the cusp of amyloidosis reduced cortical Abeta deposit burden by 31% and Abeta levels by 30-37%, which was associated with cognitive improvements. In contrast, treatment from 19 months, when pathology is well established, was not immunogenic and therefore did not reduce Abeta burden or improve cognition. Significantly, the immunotherapy in the 11-24 months treatment group, that reduced Abeta burden, did not increase cerebral bleeding or vascular Abeta deposits in contrast to several Abeta antibody studies. These findings indicate that our approach age-dependently improves cognition and reduces Abeta burden when used with an adjuvant suitable for humans, without increasing vascular Abeta deposits or microhemorrhages.European Journal of Neuroscience 12/2006; 24(9):2530-42. · 3.63 Impact Factor -
Chapter: Clusterin and Alzheimer’s Disease
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ABSTRACT: Clusterin (apolipoprotein J) is a ubiquitous multifunctional glycoprotein with the capability to interact with a broad spectrum of molecules, among them the Alzheimer’s Aβ peptide. Due to its colocalization with fibrillar deposits in systemic and cerebral amyloid disorders, clusterin is also considered an amyloid-associated protein. Although no genuine function has been attributed to this protein so far, it has been implicated in a wide variety of physiological and pathological processes, a role that may vary according to the protein maturation, sub-cellular localization, and the presence of certain tissue- or cell-specific factors. This review focuses on the importance of clusterin in health and disease conditions, with particular emphasis in its role in Aβ amyloidosis and other disorders of protein folding.11/2006: pages 273-298; -
Article: Plaque-associated overexpression of insulin-degrading enzyme in the cerebral cortex of aged transgenic tg2576 mice with Alzheimer pathology.
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ABSTRACT: It was proposed that insulin-degrading enzyme (IDE) participates in the clearance of amyloid beta (Abeta) in the brain, and its low expression or activity may be relevant for the progression of Alzheimer disease. We performed a longitudinal study of brain level, activity, and distribution of IDE in transgenic mice (Tg2576) expressing the Swedish mutation in human Abeta precursor protein. At 16 months of age, Tg2576 showed a significant 2-fold increment in IDE protein level as compared with 4.5- and 11-month-old animals. The peak of IDE was in synchrony with the sharp accumulation of sodium dodecyl sulfate-soluble Abeta and massive Abeta deposition into plaques. At this stage, IDE appeared surrounding Abeta fibrillar deposits within glial fibrillar acidic protein-positive astrocytes, suggesting that it was locally overexpressed during the Abeta-mediated inflammation process. When primary astrocytes were exposed to fibrillar Abeta in vitro, IDE protein level increased as compared with control, and this effect was reduced by the addition of U0126, a specific inhibitor of the ERK1/2 mitogen-activated protein kinase cascade. We propose that in Tg2576 mice and in contrast to its behavior in Alzheimer brains, active IDE increases with age around plaques as a component of astrocyte activation as a result of Abeta-triggered inflammation.Journal of Neuropathology and Experimental Neurology 11/2006; 65(10):976-87. · 4.26 Impact Factor -
Article: Studies on the first described Alzheimer's disease amyloid beta mutant, the Dutch variant.
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ABSTRACT: Amyloid protein deposited in cerebral vessel walls and diffuse plaques of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D), is similar to the 40-42 residues amyloid beta (Abeta) in vessel walls and senile plaques in brains of patients with Alzheimer's disease (AD), Down's syndrome, and familial and sporadic cerebral amyloid angiopathy (CAA). In 1990 we sequenced the amyloid beta-protein precursor (AbetaPP) gene from HCHWA-D patients revealing a single mutation that results in an amino acid substitution, Abeta E22Q. Subsequent identification of additional mutations in the AbetaPP gene in familial AD (FAD) pedigrees revealed that whereas substitutions in the middle of Abeta, residues Abeta21-23, are predominantly vasculotropic, those found amino- or carboxyl-terminal to the Abeta sequence within AbetaPP enhance amyloid parenchymal plaque deposition. Studies of transfected cells showed that substitutions amino- or carboxyl-terminal to Abeta lead to either greater Abeta production or to enhanced secretion of the more hydrophobic thus more fibrillogenic Abeta1-42. Substitutions in the center of Abeta facilitate rapid aggregation and fibrillization, slower clearance across the blood-brain barrier and perivascular drainage to the systemic circulation, possibly higher resistance to proteolysis, and enhanced toxicity towards endothelial and smooth muscle cells. However, most AD patients have no genetic defects in AbetaPP, indicating that other factors may alter Abeta production, conformation, and/or clearance initiating the disease process.Journal of Alzheimer's disease: JAD 02/2006; 9(3 Suppl):329-39. · 3.74 Impact Factor -
Article: Familial Danish dementia: co-existence of Danish and Alzheimer amyloid subunits (ADan AND A{beta}) in the absence of compact plaques.
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ABSTRACT: Familial Danish dementia is an early onset autosomal dominant neurodegenerative disorder linked to a genetic defect in the BRI2 gene and clinically characterized by dementia and ataxia. Cerebral amyloid and preamyloid deposits of two unrelated molecules (Danish amyloid (ADan) and beta-amyloid (Abeta)), the absence of compact plaques, and neurofibrillary degeneration indistinguishable from that observed in Alzheimer disease (AD) are the main neuropathological features of the disease. Biochemical analysis of extracted amyloid and preamyloid species indicates that as the solubility of the deposits decreases, the heterogeneity and complexity of the extracted peptides exponentially increase. Nonfibrillar deposits were mainly composed of intact ADan-(1-34) and its N-terminally modified (pyroglutamate) counterpart together with Abeta-(1-42) and Abeta-(4-42) in approximately 1:1 mixture. The post-translational modification, glutamate to pyroglutamate, was not present in soluble circulating ADan. In the amyloid fractions, ADan was heavily oligomerized and highly heterogeneous at the N and C terminus, and, when intact, its N terminus was post-translationally modified (pyroglutamate), whereas Abeta was mainly Abeta-(4-42). In all cases, the presence of Abeta-(X-40) was negligible, a surprising finding in view of the prevalence of Abeta40 in vascular deposits observed in sporadic and familial AD, Down syndrome, and normal aging. Whether the presence of the two amyloid subunits is imperative for the disease phenotype or just reflects a conformational mimicry remains to be elucidated; nonetheless, a specific interaction between ADan oligomers and Abeta molecules was demonstrated in vitro by ligand blot analysis using synthetic peptides. The absence of compact plaques in the presence of extensive neuro fibrillar degeneration strongly suggests that compact plaques, fundamental lesions for the diagnosis of AD, are not essential for the mechanism of dementia.Journal of Biological Chemistry 12/2005; 280(44):36883-94. · 4.77 Impact Factor
Top co-authors
Top Journals
Institutions
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1991–2011
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New York University USA
- • Department of Pathology
- • Department of Neurology
- • Medicine
- • Department of Psychiatry
New York City, NY, USA
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2010
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University of Tsukuba
- Department of Neurology
Tsukuba, Ibaraki-ken, Japan
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1994–2009
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State University of New York Downstate Medical Center
- Department of Pathology
Brooklyn, NY, USA
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2006
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Nathan Kline Institute
Orangeburg, NY, USA
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2005
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University of Buenos Aires
- Departamento de Química Biológica
Buenos Aires, Buenos Aires F.D., Argentina -
Fundación Instituto Leloir
Buenos Aires, Buenos Aires F.D., Argentina -
Instituto de Salud Carlos III
Madrid, Madrid, Spain
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1992–2005
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CUNY Graduate Center
New York City, NY, USA
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2002
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University College London
- Department of Molecular Neuroscience
London, ENG, United Kingdom -
University of Southern California
- Department of Neurological Surgery
Los Angeles, CA, USA -
Indiana University-Purdue University Indianapolis
- Department of Pathology and Laboratory Medicine
Indianapolis, IN, USA
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1999
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New York State Institute for Basic Research in Developmental Disabilities
New York City, NY, USA
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