Michael G. Heckman

Comparison of desmoid tumor PRO information between baseline, 6-month, and 24-month follow-up.

Representativeness of Study Participants.

A Scatterplot demonstrating correlation between the early changes in post-contrast signal intensity and 24-month tumor volume.

A Scatterplot demonstrating correlation between the early changes in T2 signal intensity and 24-month tumor volume.

Comparison of SF-12 and VAS information between baseline, 6-month, and 24-month follow-up.

Purpose:The purpose of this pilot study was to examine the clinical efficacy and safety of serial triamcinolone injections for the treatment of desmoid tumors.Patients and Methods:Nine patients were enrolled into this prospective study and underwent three serial ultrasound-guided triamcinolone injections (120 mg) at 6-week intervals. MRI was compared at baseline and every 6 months, out to 24 months. Safety and tolerability were assessed by clinical evaluation and questionnaires, including the 12-item short form survey (SF-12), visual analog scale (VAS), and desmoid patient-reported outcome (PRO) tool.Results:At 24 months, 8 (88.9%) patients demonstrated a reduction in the volume of their tumor while 1 (11.1%) enlarged. Median tumor volume change was −26.9% (−81.1% to 34.6%; P = 0.055) All 9 tumors remained stable based on World Health Organization criteria, whereas 2 (22.2%) demonstrated partial response based on RECIST. There was a significant decrease in the tumor:muscle postcontrast mean signal intensity ratio at 6 months (P = 0.008) and 24 months (P = 0.004). There was a similar decrease in the tumor:muscle T2 mean signal intensity ratio at 24 months (P = 0.02). We found no difference in the SF-12 and VAS scores, but there were significant improvements in the desmoid PRO.Conclusions:Treatment of desmoid tumors with serial triamcinolone injections appears safe and well tolerated by patients, with a 22% partial response based on RECIST. Further research is needed to confirm our results and determine factors predictive of response.

Objective: Lewy body disease (LBD) is a complex neurodegenerative disorder characterized by the accumulation of misfolded α‐synuclein in the brain. Neuroinflammation has long been implicated in LBD pathogenesis, and recent genetic studies in Parkinson's disease (a clinical manifestation of LBD) have shown consistent association with the human leukocyte antigen (HLA) gene complex. Here, we assessed whether variation in HLA alleles influences neuropathological burden in a neuropathologically‐defined series of LBD cases. Methods: We conducted a comprehensive analysis of HLA allelic variants in a cohort of 539 LBD cases of European descent from the Mayo Clinic brain bank. High‐resolution whole‐genome sequencing was used, and the HLA alleles of each sample were called using the HLA*LA tool and assessed for association with neuropathological outcomes. Results: Our analysis identified 1 significant ( P < 3.43 × 10 ⁻⁵ ) and 4 suggestive ( P < 0.001) associations between certain HLA alleles and specific neuropathological outcomes in LBD, suggesting a potential role for HLA‐mediated immune mechanisms in disease progression and subtype differentiation. Specifically, HLA‐DPB1*06:01 was significantly associated with lower Lewy body counts in the parahippocampal gyrus ( P = 3.30 × 10 ⁻⁵ ), with weaker and suggestive associations observed in the middle frontal ( P = 1.80 × 10 ⁻⁴ ) and inferior parietal gyrus ( P = 6.33 × 10 ⁻⁴ ). Additionally, although only suggestive, HLA‐DRB1*11:01 correlated with a lower Thal amyloid phase ( P = 1.56 x 10 ⁻⁴ ), and HLA‐B*15:01 correlated with an increased risk of diffuse LBD ( P = 7.58 x 10 ⁻⁴ ). Interpretation: This study provides a detailed evaluation of the relationship between HLA alleles and LBD pathology, highlighting the importance of immune‐related genetic factors in the etiology of LBD. ANN NEUROL 2026;99:492–501

Background/Goal: Parkinson’s disease (PD) disrupts dopaminergic transmission, leading to motor deficits and altered activity in the primary motor cortex (M1). While M1 modulation is critical for motor control, its response to dopaminergic degeneration and treatment remains unclear. This study aimed to characterize M1 neuronal activity and motor behavior in hemiparkinsonian rats using in vivo calcium imaging across naïve, lesioned, and levodopa-treated states. Methods: Thirteen Sprague Dawley rats were injected with GCaMP6f in the M1 and implanted with a GRIN lens and guide cannula targeting the medial forebrain bundle. Calcium imaging and motor behavior were assessed longitudinally using a single pellet reaching test (SPRT) before and after unilateral 6-hydroxydopamine (6-OHDA) lesioning and subsequent levodopa/carbidopa treatment. Dopaminergic lesion severity was quantified via tyrosine hydroxylase immunohistochemistry. Calcium event frequency and influx were analyzed with CNMF-E and statistical modeling. Results: Levodopa treatment improved fine motor performance as shown by a significant reduction in grasp errors (mean difference: −8.91, 95% CI: −16.66 to −1.16, p = 0.031) and increased reaching duration (mean difference: 4.13, 95% CI: 0.94 to 7.32, p = 0.019) compared to the lesioned state. M1 calcium activity showed modulation dependent on lesion severity: low-lesion rats exhibited reduced event frequency (mean difference: 0.04 Hz, 95% CI: 0.001 to 0.08, p = 0.045) and increased influx post-lesion (mean difference: −0.20 z·s, 95% CI: −0.38 to −0.02, p = 0.038), while high-lesion rats showed increased influx only after levodopa treatment (mean difference: −0.34 z·s, 95% CI: −0.52 to −0.16, p = 0.003). Correlation analyses revealed that calcium influx, but not frequency, was negatively correlated with lesion severity during levodopa treatment (Spearman r = −0.857, p = 0.024). Conclusion: M1 neuronal activity appears to be differentially modulated by dopaminergic degeneration and levodopa treatment in a lesion-dependent manner. These preliminary findings suggest dynamic cortical responses in PD and support the utility of calcium imaging for monitoring circuit-level changes in disease and therapy. Further research with larger cohorts and complementary methodologies will be necessary to validate and extend these observations.

The APOE (apolipoprotein E) ε4 allele is the strongest known genetic risk factor for sporadic Alzheimer disease (AD) and for brain amyloidosis, an early marker of disease pathophysiology. However, APOE ε4 is present in only 25% of the general population and is by itself inadequate for explaining susceptibility to amyloid accumulation or AD diagnosis. Existing studies have been limited by potential confounding due to inclusion of individuals carrying APOE ε4 or ε2 (which has a modest protective association). We hypothesized that genome-wide association study (GWAS) and genetic risk score (GRS) analyses in APOE ε3/ε3 individuals would uniquely identify novel predictors of β-amyloid pathology in older adults. We analyzed data from the Mayo Clinic Study of Aging (MCSA), Alzheimer's Disease Neuroimaging Initiative (ADNI), and Rush Religious Orders Study and Memory and Aging Project. Frequency of APOE ε3/ε3 in those samples ranged from 48% to 61%. A GWAS was performed across 1,496 individuals with amyloid PET to identify candidate variants for GRS generation. Postmortem neuropathologic data (N = 710) were used to refine the variant list to capture high-likelihood true associations. An independent sample (N = 641) with plasma p-tau₁₈₁ data was used for validation. The GWAS identified previously implicated (e.g., PICALM and RBFOX1) and novel potential associations with amyloid PET burden. A non-APOE GRS of top variants was strongly associated with amyloid PET levels in the MCSA (p = 4.34 × 10⁻⁹, β = 5.88) and ADNI (p = 1.87 × 10⁻⁸, β = 12.1) cohorts. In both cohorts, this non-APOE amyloid GRS outperformed a comparator GRS (based on variants associated with clinically diagnosed AD dementia risk) in explaining phenotypic variation. The non-APOE amyloid GRS was also associated with postmortem neuropathologic β-amyloid and neurofibrillary tangle burden and in an independent sample was associated with plasma p-tau₁₈₁ concentrations (a robust indicator of cerebral amyloidosis). Our non-APOE amyloid GRS, which appropriately includes variants associated with amyloid deposition in APOE ɛ4/ɛ2 noncarriers, may advance personalized prediction of genetic susceptibility to β-amyloid accumulation within the large segment of the population that is APOE ε3/ε3. This may have future implications for risk modification, trial enrollment, and treatment selection.