About

Thomas Francis Tropea, DO, MPH, MSTR, is an Adjunct Assistant Professor of Neurology at the University of Pennsylvania's Perelman School of Medicine. He is affiliated with the Department of Neurology and is based at the university's Philadelphia campus. Dr. Tropea's educational background includes a Bachelor of Science in Biopsychology from Tufts University, obtained in 2005, a Doctor of Osteopathic Medicine from the University of New England College of Osteopathic Medicine in 2011, a Master of Public Health also from the University of New England in 2011, and a Master’s in Translational Research from the University of Pennsylvania in 2018. His research focuses on neurodegenerative diseases, with contributions to biomarker discovery, genetic and phenotypic characterization of Parkinson's disease, and the development of diagnostic tools for neurological disorders. Dr. Tropea has authored multiple publications in reputable journals, emphasizing his active engagement in advancing understanding and diagnosis of neurodegenerative conditions.

Research topics

• Medicine
• Psychiatry
• Internal medicine
• Family medicine
• Environmental health
• Psychology
• Oncology
• Surgery
• Pathology
• Biology
• Demography
• Bioinformatics
• Gerontology

Selected publications

• CSF α-Synuclein Seed Amplification Assays and Skin Immunofluorescence

  Neurology · 2026-01-13 · 2 citations

  article

  The development of biomarkers capable of reliably detecting pathologic forms of α-synuclein (aSyn) in vivo marks a significant step forward in the field of neurodegeneration. Over the recent years, CSF aSyn seed amplification assays (aSyn-SAA) and skin biopsy phospho-aSyn immunofluorescence (skin aSyn-IF) testing were developed that detect pathologic aSyn seeds and phosphorylated aSyn aggregates, respectively, in patients with synucleinopathies, which include Parkinson disease, dementia with Lewy bodies, and also multiple system atrophy. High rates of positivity have also been documented in research participants at a risk of developing future aSyn-related disease (e.g., hyposmia and REM sleep behavior disorder), as well as other contexts. These assays have numerous potential applications in research settings and clinical care. Here, we review the currently published evidence supporting CSF aSyn-SAA and skin aSyn-IF testing and discuss their potential research applications in clinical trials. As CSF aSyn-SAA and skin aSyn-IF testing is now commercially available to clinicians in nonresearch settings, we also explore their current utility and limitations as diagnostic tools and call for the development of a formal clinical use guidelines. We also highlight where critical knowledge gaps remain and explore emerging developments related to these assays.

  PublisherDOI

• Novel <i>PCDH12</i> pathogenic missense variants cause neurodevelopmental disorders with ocular malformation

  medRxiv · 2026-03-06

  articleOpen access

  Abstract Protocadherin-12 (PCDH12), a cell-adhesion protein belonging to the non-clustered protocadherin family, plays a crucial role in the establishment and regulation of neuronal connections and communication. Bi-allelic loss-of-function (LoF) variants in the PCDH12 gene have been associated with several neurodevelopmental disorders (NDDs) such as diencephalic-mesencephalic junction dysplasia syndrome, cerebral palsy, and cerebellar ataxia, often accompanied by ocular abnormalities. However, genotypes exhibit variable expressivity. Affected individuals sharing the same PCDH12 variant presenting differing phenotypic severities have posed major challenges towards identification of the underlying pathogenic mechanisms. Here, we report three affected individuals from two families, each harbouring non-truncating pathogenic missense variants in PCDH12 . The patients are compound heterozygous, with each individual carrying one extracellular [c.1742T&gt;G (p.Val581Gly) and c.1861_2del/insCA (p.Ile621His)] and one intracellular variant [c.3370C&gt;T (p.Arg1124Cys) and c.3445G&gt;A (p.Asp1149Asn] on each allele. The children present with a range of phenotypes similar to those associated with LoF variants. One child exhibited microcephaly and seizures, while the two siblings displayed developmental delays and severe behavioral disorders. All three children experienced some degree of visual impairment. The missense variants provided new insights into the neurodevelopmental consequences of compromised PCDH12 function by distinguishing the specific consequences associated with dysfunction in the extracellular versus intracellular domains of PCDH12. All identified missense variants are predicted to be deleterious and destabilizing. The expression of PCDH12 in HEK293T and HeLa cells demonstrated that PCDH12 is expressed effectively, regardless of the presence of missense variants. However, the extracellular variants p.Val581Gly and p.Ile621His compromised the stability of PCDH12’s homophilic adhesion. Additionally, we found evidence of an interaction between PCDH12 and the extracellular domain of the epilepsy-associated PCDH19 protein. PCDH12 extracellular missense variants also affect PCDH19 stability. Our study provides evidence that PCDH12 mediates both homophilic and heterophilic interactions. Our findings also highlight the importance of stable PCDH12-mediated adhesion, emphasizing the need to further study the functional consequences of PCDH12 missense variants on brain and visual system development.

  PublisherOA PDFDOI

• Clinical and imaging characteristics of Parkinson’s disease with negative alpha-synuclein seed amplification assay

  medRxiv · 2025-10-03 · 1 citations

  preprintOpen access

  Abstract Background The CSF alpha-synuclein seed amplification assay (CSFasynSAA) detects alpha-synuclein aggregation in over 90% of individuals with sporadic PD (sPD). However, the clinical characteristics of sPD with negative CSFasynSAA remain undefined. Objectives Describe clinical and neuroimaging characteristics of CSFasynSAA negative sPD individuals in the Parkinson’s Progression Markers Initiative (PPMI). Methods We identified sPD PPMI participants with a negative CSFasynSAA (SAA negative, n=80) or positive CSFasynSAA (SAA positive, n=856) result at baseline. For comparative analysis between groups we used a reduced dataset (n=79 SAA negative and n=237 SAA positive) propensity-score matched on age, sex, and time since clinical diagnosis. Clinical parameters, DAT-SPECT, and MRI brain volumetrics were analyzed. Results The SAA negative and matched SAA positive groups had similar motor performance on the MDS-UPDRS-part III and similar cognitive performance on the MoCA at baseline. The proportion with severe hyposmia was 12% for SAA negative versus 73% for SAA positive ( p &lt; 0.001). Per PPMI enrollment criteria all participants were classified as having an abnormal DAT-SPECT. There were no significant differences in median quantitative DAT-SPECT measures between groups. The SAA negative group showed a higher degree of atrophy in subcortical brain regions including substantia nigra. Longitudinally, 14.3% of SAA negative participants had a change in diagnosis, versus 0.9% of SAA positive participants. Conclusions At baseline, SAA negative sPD PPMI participants have a substantially lower rate of hyposmia, but otherwise cannot be readily distinguished from SAA positive participants based on clinical characteristics. However, SAA negative participants have a greater degree of subcortical brain atrophy, and approximately 1 out of 6 SAA negative participants received a change in diagnosis.

  PublisherOA PDFDOI

• Calcium modulating ligand confers risk for Parkinson's disease and impacts lysosomes

  Annals of Clinical and Translational Neurology · 2025-03-07 · 1 citations

  articleOpen access

  OBJECTIVE: Several genetic loci known to confer risk for Parkinson's disease (PD) function in lysosomal pathways. We systematically screened common variants linked to PD risk by genome-wide association studies (GWAS) for impact on cerebrospinal fluid (CSF) proteins reflecting lysosomal function. METHODS: Starting with 525 candidate gene-single nucleotide polymorphism (SNPs) pairs nominated by Mendelian randomization from published PD GWAS, we filtered SNPs for downstream evaluation, based on strength of association with PD and impact on brain gene expression. We genotyped top SNPs in 173 PD participants, adding three SNPs capturing variation at the TMEM106B, CTSB, and RAB29 loci, encoding genes with known lysosomal function. In the same 173 individuals, we measured 15 CSF proteins (nine lysosomal proteins and six other proteins implicated in neurodegeneration) by parallel reaction monitoring mass spectrometry. We tested SNPs for association with lysosomal proteins. For our top SNP associating with multiple lysosomal proteins, we characterized expression of its target gene CAMLG in human brain tissue. RESULTS: Sixteen SNPs emerged from our analysis of GWAS-nominated loci. Genotypes at rs12657663 (CAMLG) associated with CSF levels of multiple lysosomal markers (cathepsin F, cathepsin L, hexosaminidase B, and tripeptidyl peptidase I) and genotypes at rs7910668 (ITGA8) with CSF levels of cathepsin B. The protein encoded by CAMLG, calcium modulating ligand (CAML), is highly expressed in neurons of multiple human brain regions, with higher expression in Lewy body disease cases. INTERPRETATION: Systematic analysis of PD risk loci nominates CAMLG as a neuronally expressed risk gene with effects on lysosomes.

  PublisherOA PDFDOI

• Tau Burden is Best Captured by Magnitude and Extent: Tau-MaX as a Measure of Global Tau

  medRxiv · 2025-01-14 · 9 citations

  preprintOpen access

  Abstract Tau exhibits change in both spatial extent and density of pathology along the Alzheimer’s disease (AD) spectrum with each aspect contributing to the overall burden of pathological tau. Nevertheless, studies using Tau PET have measured either magnitude using standardized uptake value ratios (SUVRs) or extent using number of Tau+ regions. We hypothesized that combining these two dimensions into a single measure of Magnitude and eXtent, Tau-MaX, would provide improved quantification of global tau burden as well as allowing for a region-agnostic measure of global tau burden that does not require a pre-specified region of interest (ROI) or meta-ROI. To test this hypothesis, we analyzed 18 F-flortaucipir PET scans from local and national consortium data (n=1077 participants total) and used Gaussian-mixture models for data from 64 brain regions, to define both tau positivity and magnitude. We examined cross-sectional and longitudinal change in Tau-MaX across the Alzheimer’s disease (AD) spectrum and compared the association of Tau-MaX, magnitude, and extent with plasma p-tau 217 and global cognition. We also compared Tau-MaX using a global, region-agnostic approach to temporal lobe or Braak stage meta-ROIs. Whereas separate assessments of extent and magnitude across the disease spectrum found earlier increases in Tau spatial extent and later increases in magnitude, Tau-MaX was able to dynamically capture this shift demonstrating a stronger association with extent in the preclinical stage and a stronger association with magnitude in clinical stages. Global Tau-MaX differed between disease stages cross-sectionally and changed over time in all stages of disease. Further, Tau-MaX significantly improved associations with plasma p-tau 217 and global cognition compared to magnitude or extent alone. Finally, global measures of Tau-MaX performed similarly to meta-ROI measures of Tau-MaX. Together, these findings indicate that combining magnitude and extent provides a robust measure of global tau burden that changes throughout the disease course and is associated with blood-based biomarkers and cognition. This measure may be of particular use for disease staging, as well as serving as an outcome measure to monitor response to therapeutic intervention.

  PublisherOA PDFDOI

• It is time to share Alzheimer biomarker results in dementia with Lewy bodies

  Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · 2025-07-01 · 5 citations

  articleOpen accessSenior author

  There are increasing calls for sharing individual biomarker results with participants in dementia research. No studies investigate returning Alzheimer's disease (AD) biomarker results to individuals with syndromic dementia with Lewy bodies (DLB) even though most of these individuals have both pathologies. This perspective argues that AD biomarkers are valid, interpretable, and actionable, particularly relating to expected prognosis and treatment effects, in people with DLB. Thus, there is an ethical imperative to study AD biomarker result sharing in these patients. This will require revising current disclosure practices. Areas of need include unique pre- and post-test education and careful assessment of the readiness to receive results and post-result responses in people with DLB given the frequency of neuropsychiatric symptoms in this group. Studying responses to sharing AD biomarkers in people with DLB will also inform other dementia settings (e.g., returning synuclein results to individuals with syndromic AD) and neurodegenerative diseases more broadly. Highlights: There are increasing calls for biomarker result sharing in dementia research.No processes exist to guide result sharing in dementia with Lewy bodies (DLB).Alzheimer biomarker results in DLB are valid, interpretable, and actionable.Research is needed on the methods and effects of sharing with people with DLB.Research is needed for sharing evidence of co-pathology across neurodegenerations.

  PublisherOA PDFDOI

• Comparison of plasma p‐tau217/Aβ42, p‐tau217, and Aβ42/Aβ40 biomarkers by race to detect Alzheimer's disease

  Alzheimer s & Dementia · 2025-08-01 · 19 citations

  articleOpen access

  INTRODUCTION: In clinically and racially diverse training and test sets, we evaluated and validated Alzheimer's disease (AD) plasma biomarkers: phosphorylated tau-217 (p-tau217), amyloid beta 1-42/1-40 (Aβ42/Aβ40), and p-tau217/Aβ42. METHODS: F-florbetapir positron emission tomography (PET) data. In the training set (n = 289; 28% pBlack), we used receiver-operating characteristic (ROC) analysis to calculate two cut points (0.95 sensitivity and specificity) to detect amyloid PET positivity. Cut points were validated in an independent test set (n = 846; 12% pBlack). RESULTS: In the test set, plasma p-tau217/Aβ42 had the highest accuracy (pBlack: 0.88, pWhite: 0.91) and lowest proportion of intermediate classifications (≤0.16), with no classification difference by race (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.66-2.95, p = 0.33). False negatives were more likely to be cognitively normal (vs mild cognitive impairment [MCI]; OR = 7.79, 95% CI = 2.33-40.81, p = 5.1e-05) than correct classifications. DISCUSSION: Plasma p-tau217/Aβ42 had high accuracy to detect AD, with comparable performance across race. HIGHLIGHTS: , p-tau217, and Aβ42/Aβ40 in diverse training and test sets. In models, race × amyloid PET interactions were not significant. Plasma p-tau217/Aβ42 had the highest accuracy in people who self-identified as Black/African American (pBlack; 0.88) and people who self-identified as White (pWhite; 0.91). Plasma p-tau217/Aβ42 had the lowest proportion of intermediate cases (range = 0.09-0.16). False negatives were more likely to have normal cognition, female sex, and high body mass index.

  PublisherOA PDFDOI

• Blood α‐Synuclein Separates Parkinson's Disease from Dementia with Lewy Bodies

  Annals of Neurology · 2025-06-16 · 4 citations

  articleOpen access

  OBJECTIVE: Aggregation of misfolded α-synuclein (aSyn) within the brain is the pathologic hallmark of Lewy body diseases (LBDs), including Parkinson's disease (PD), and dementia with Lewy bodies (DLB) disease. Although evidence exists for aSyn "strains," conformations with distinct biological properties, biomarkers for PD versus DLB are lacking. Here, we used monoclonal antibodies selective for two different in vitro aSyn species - termed strain A and B - to evaluate human brain tissue, cerebrospinal fluid (CSF), and plasma. METHODS: Using these antibodies, we characterized specific aSyn species in human specimens from neurologically normal individuals and individuals with LBD using enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemistry. We also characterized aSyn species immunoprecipitated from brain lysate or plasma with these antibodies using seed amplification assays (SAAs) and a cellular model. RESULTS: Surprisingly, levels of strain A and B aSyn species were higher in plasma from individuals with PD compared to DLB in 2 independent cohorts. Lower levels of plasma aSyn strain A species predicted a faster rate of cognitive decline in individuals with PD. Furthermore, strain A and strain B aSyn species were undetectable in CSF, and their levels in brain versus plasma did not correlate. Moreover, plasma aSyn species isolated by aSyn strain antibodies could template aSyn fibrillization, and they could seed formation of aSyn inclusions in cells. INTERPRETATION: Our findings suggest that circulating plasma aSyn strains may impact LBD clinical presentation, particularly cognition. The enrichment of these aSyn species in plasma but not CSF also suggests a potential source outside the brain. ANN NEUROL 2025;98:682-698.

  PublisherOA PDFDOI

• Patient‐reported outcomes for remote and in‐person visits for genetic counseling in adult neurology

  Journal of Genetic Counseling · 2025-05-23 · 2 citations

  articleOpen access

  At our center, we offer clinical genetic counseling (GC) visits for adults with a personal and/or family history of neurologic disease. Here, we report patient experience and outcomes from different visit modalities (e.g., in person, videoconferencing, and telephone) in clinical neurogenetics. Individuals who completed a GC visit in the Neurology Department at the University of Pennsylvania between January 2021 and January 2023 were surveyed after an initial evaluation and/or a disclosure visit. Questionnaires included items validated to measure satisfaction with GC, satisfaction with telehealth, and patient empowerment. Two hundred and ninety-nine individuals submitted 347 survey responses, representing a response rate of 42% (initial) and 31% (disclosure) for each of the surveys. Most responders completed their initial visit in person, while most completed their disclosure visit remotely via videoconferencing or telephone. Patient satisfaction with GC did not differ between visit modalities. For initial visits, telehealth satisfaction was higher for visits regarding the consideration of predictive testing compared to diagnostic testing. For follow-up visits, telehealth satisfaction was higher for videoconferencing compared to telephone disclosure. A majority of responders (69%-78%) reported interest in utilizing telehealth in the future if their genetic counselor thought it was appropriate and a majority of responders (65%-79%) indicated a preference for a combination of in-person and telehealth visits. Individuals who completed an initial visit in person were more likely to decline interest in future telehealth use. This study allowed for some comparison between visit modalities, but more research is needed to understand individuals' preferences and guide recommendations for GC service delivery.

  PublisherOA PDFDOI

• An Open‐Label Pilot Study to Examine the Safety, Tolerability and Efficacy of Deutetrabenazine in Isolated Dystonia

  Movement Disorders Clinical Practice · 2025-01-04 · 4 citations

  articleOpen access

  BACKGROUND: Dystonia may respond to VMAT2 inhibition. OBJECTIVES: Providing pilot data on the safety, tolerability, and efficacy of deutetrabenazine in non dopa-responsive dystonia. METHODS: Deutetrabenazine was titrated by adults with isolated dystonia. Primary study endpoints included the proportion who maintained the individual, maximum tolerated dose for 6 weeks, and how many titrated to 48 mg/day. Secondary endpoints included rates of QTc prolongation/arrhythmias, suicidality, excessive daytime sleepiness, cognitive decline, and drug-induced parkinsonism. Exploratory endpoints for clinical efficacy were assessed. RESULTS: Among 15 participants, four (26.7%) withdrew early and six (40%) titrated to 48 mg/day. Common adverse events included fatigue and diarrhea. Secondary safety endpoints did not change significantly, but MDS-UPDRS III scores worsened by ≥3 points in seven participants (46.7%). PGI-C and the blinded CGI-C and GDS improved in three women with blepharospasm. CONCLUSIONS: Most participants tolerated deutetrabenazine for 6 weeks, and those with blepharospasm may have benefitted from its use.

  PublisherOA PDFDOI

Recent grants

• The Role of Alzheimer's Disease Genetic Risk in Predicting Parkinson's Disease Dementia

  NIH · $985k · 2020–2025

Frequent coauthors

• Alice Chen‐Plotkin

  University of Pennsylvania

  71 shared

• Barry E. Kosofsky

  Cornell University

  59 shared

• Daniel Weintraub

  Veterans Health Administration

  53 shared

• Anjali M. Rajadhyaksha

  Weill Cornell Medicine

  44 shared

• David J. Irwin

  University of Pennsylvania

  38 shared

• Katheryn A.Q. Cousins

  California University of Pennsylvania

  36 shared

• Leslie M. Shaw

  University of Pennsylvania

  34 shared

• Andrew Siderowf

  University of Pennsylvania

  34 shared

Education

• BS

  Tufts University

• MSTR, Translational Medicine and Therapeutics

  University of Pennsylvania

  2018

• DO

  University of New England College of Osteopathic Medicine

  2011

Awards & honors

• GPNMB Biomarker Levels in GBA1 Carriers with Lewy Body Disor…
• Hope vs. Hype II: It is time to offer pre-symptomatic geneti…
• Genetic and phenotypic characterization of Parkinson's disea…
• α-Synuclein Conformations in Plasma Distinguish Parkinson's…
• Tau maturation in the clinicopathological spectrum of Lewy b…