Complementary choroid plexus and locus coeruleus dysfunction in Parkinson's disease progression

Nucleus basalis of Meynert integrity is associated with cognitive dysfunction in Parkinson's disease independently of locus coeruleus degeneration

Choroid plexus volume in pathology-confirmed Alzheimer's disease

Introduction The choroid plexus (CP) increases in volume across the Alzheimer’s disease (AD) continuum, suggesting its potential as a clearance-related biomarker. However, few studies have examined ante-mortem CP volume in relation to post-mortem AD pathology, the gold standard for diagnosis. Methods Participants who had structural magnetic resonance imaging and post-mortem pathology, with an interval of ≤ 5 years between imaging and death, were examined. Normalized CP volume (NCPV) was semi-automatically segmented from the lateral ventricles and analyzed using Bayesian linear regression to estimate associations with cognitive impairment (CI), AD pathology, and relevant clinical/demographic data. Results Intermediate and high levels of AD pathology and CI were associated with larger NCPV, whereas female sex was associated with lower NCPV. Subgroup analyses showed larger NCPV in individuals with greater CI despite comparable levels of AD pathology. Discussion These findings link CP enlargement to neuropathologically confirmed AD burden and CI, supporting further investigation of CP structure and function in AD.

Local brain network alterations in prodromal and De Novo Parkinson's disease: basal ganglia functional connectivity mediates the association between regional homogeneity and motor manifestations.

BACKGROUND AND OBJECTIVE Recently, three motor phases of Parkinson's disease (PD) have been proposed (a silent period when nigrostriatal loss begins, a prodromal motor period with subtle focal manifestations, and clinical PD) accompanying the early loss of nigrostriatal dopaminergic pathways and the dysfunction of the basal ganglia (BG) loop, which produce vital network alterations that impact motor coordination. However, the relationships among local brain abnormalities, BG-based functional connectivity (FC) and motor performance in early PD remain unclear. Thus, our study aims to characterize local brain activity dysfunction and large-scale network disorganization, and further explore the potential neural pathway from local dysrhythmia to network-level dysfunction ultimately to clinical motor deficits. METHODS We enrolled 32 healthy controls (HC), 20 prodromal PD (pPD) patients without mild motor signs (pPD-NMMS), 42 pPD patients with MMS (pPD-MMS), and 58 de novo PD (dPD) patients. We calculated the regional homogeneity (ReHo) and FC values of BG subregions and differences among groups. Furthermore, correlation analyses between ReHo, FC values, and motor sub-scores were analyzed. Additionally, a mediation analysis was conducted to investigate the mediating function of FC-distinct brain regions between ReHo values and motor performance. RESULTS Compared with the other groups, pPD-NMMS patients had increased ReHo values in the right lingual gyrus (LING). However, the pPD-MMS group had increased FC values in the left globus pallidus (GP), the bilateral ventromedial putamen (vmPu) to sensorimotor regions, and the left vmPu, the left dorsal caudate (dCa) to visual cortex regions. Both ReHo values in the right LING and FC values of the left GP and the left vmPu were correlated with tremor scores. Eventually, mediation analyses revealed that FC values between the left GP and the right postcentral gyrus (PoCG), and between the left vmPu and the right inferior occipital gyrus (IOG) mediated the relationship between ReHo values in the right LING and tremor scores. CONCLUSION Along with the transition from the prodromal to the manifested period and the development of motor signs, network alterations of BG loop may play an important mediating role between local alterations in occipital-related brain regions and tremor performance.

Neural substrates of cognitive decline and tremor in neuronal intranuclear inclusion disease: a morphometric MRI study

Striatal Tau Pathology Underlies Monoaminergic Disruption in Progressive Supranuclear Palsy

Purpose: Progressive supranuclear palsy (PSP) is a tauopathy marked by widespread tau aggregation and prominent monoaminergic dysfunction, yet the relationship between regional tau burden and monoaminergic impairment remains unclear. In this study, we determine whether regional tau burden is associated with nigrostriatal monoaminergic dysfunction in PSP using PET imaging. Patients and Methods: A subset of 20 patients with PSP and monoaminergic impairment, identified by 18F-FP-DTBZ PET, was recruited and subsequently underwent 18F-APN-1607 PET to assess tau deposition. All images were spatially normalized and analyzed based on predefined volumes of interest. Erosion-based cerebral white matter was used as the reference region to calculate standardized uptake value ratios (SUVRs) for 18F-APN-1607 PET. Results: The SUVRs of 18F-APN-1607 PET differed significantly between patients with PSP and healthy controls in the globus pallidus, substantia nigra, subthalamus nucleus, and red nucleus, while a significant difference in 18F-FP-DTBZ SUVRs was observed in all the striatal regions and substantia nigra. Regression analysis discovered negative associations between tau load and monoaminergic disruption in the putamen and caudate, whereas tau accumulation in the substantia nigra was not significantly associated with nigrostriatal impairment. Conclusions: The pallido-nigro-luysian axis and nigrostriatal system serve as sensitive targets for detecting tau deposition and monoaminergic disruption in PSP. Local striatal tau pathology and tau burden were associated with monoaminergic disruption in PSP.

Regional and Compartmental Changes Drive Progressive Patterns of Striatal Degeneration in X-Linked Dystonia Parkinsonism.

OBJECTIVE Initially described in 1976, X-linked dystonia parkinsonism (XDP) is a neurodegenerative disease that can be characterized by the presentation of dystonia and parkinsonism symptoms. Although this disease bears some resemblance to other neurodegenerative diseases in terms of symptomatology, the pathological signature of XDP is still unclear, in part because of the limited research that has been conducted. This study aims to delineate in detail the neurochemical changes occurring in the post mortem human XDP striatum and to explore their relevance to clinical symptomatology. METHODS The profiles of immunohistochemical expression of multiple spiny projection neurons and projection fiber markers was assessed in the post mortem tissue from the basal ganglia of 18 XDP and 10 neurologically normal cases. RESULTS We present evidence that degeneration of the XDP striatum follows a dorsoventral gradient, with greater vulnerability in the matrix compartment of the striatum. Considering the available clinical data of the cases investigated, we propose that this pattern of neurodegeneration is more closely associated with the duration of the disease than SINE-VNTR-Alu repeat length; however, repeat length is inversely correlated with XDP symptom onset and, therefore, influences the clinical timeline. INTERPRETATION Our findings provide a novel perspective on the pattern and degree of degeneration of the XDP striatum. We propose that the matrix compartment is more vulnerable to disease impact relative to striosomes than initially thought, and the pattern of striatal degeneration may be indicative of the breakdown of a wider cortico-basal ganglia neural circuit over the duration of the disease. ANN NEUROL 2026.