Clinicopathological correlation of cerebrospinal fluid alpha-synuclein seed amplification assay in a behavioral neurology autopsy cohort.

INTRODUCTION: Lewy body disease (LBD) is a common primary or co-pathology in neurodegenerative syndromes. An alpha-synuclein seed amplification assay (αSyn-SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala-predominant cases, is not well understood. METHODS: Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N = 56). Diagnostic performance and clinicopathological correlations were examined. RESULTS: Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3% (26/27). Sensitivity was lower in amygdala-predominant (6/14, 42.8%) and brainstem-predominant LBD (1/6, 16.7%), but early spread outside these regions (without meeting criteria for higher stage) was more common in αSyn-SAA-positive cases (6/7, 85.7%) than negative (2/13, 15.4%). DISCUSSION: In this behavioral neurology cohort, αSyn-SAA had excellent diagnostic performance for cortical LBD. In amygdala- and brainstem-predominant cases, sensitivity was lower, but positivity was associated with anatomical spread, suggesting αSyn-SAA detects early LBD progression in these cohorts. HIGHLIGHTS: A cerebrospinal fluid alpha-synuclein assay detects cortical LBD with high sensitivity/specificity. Positivity in prodromal stages of LBD was associated with early cortical spread. The assay provides precision diagnosis of LBD that could support clinical trials. The assay can also identify LBD co-pathology, which may impact treatment responses.

Dysfunctions associated with the intraparietal sulcus and a distributed network in individuals with math learning difficulties: An ALE meta-analysis.

Math learning difficulty (MLD) is a learning disorder characterized by persistent impairments in the understanding and application of numbers independent of intelligence or schooling. The current study aims to review existing neuroimaging studies to characterize the neurobiological basis in MLD for their quantity and arithmetic dysfunctions. We identified a total of 24 studies with 728 participants through the literature. Using the activation likelihood estimate (ALE) method, we found that the most consistent neurobiological dysfunction in MLD was observed in the right intraparietal sulcus (IPS) with distinct patterns of the anterior and posterior aspects. Meanwhile, neurobiological dysfunctions were also observed in a distributed network including the fusiform gyrus, inferior temporal gyrus, insula, prefrontal cortex, anterior cingulate cortex, and claustrum. Our results suggest a core dysfunction in the right anterior IPS and left fusiform gyrus with atypically upregulated functions in brain regions for attention, working memory, visual processing, and motivation, serving as the neurobiological basis of MLD.