Newest studies

Surrogate variables and the risk of overfitting in neuropsychiatric gene expression analyses

16/100 ⚠ Preprint — not yet peer-reviewed Digital health tools bioRxiv

Key finding: The reproducibility crisis in biomedical research calls for re-evaluation of how common analytic approaches affect results. +2 more findings

Scored 24 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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PDE4D inhibition activates cAMP-PKA signaling to preserve mitochondrial homeostasis and prevent neuronal necroptosis in Alzheimer's disease

16/100 ⚠ Preprint — not yet peer-reviewed Disease mechanisms Research Square

Key finding: Knocking down PDE4D in two mouse models significantly improved learning and memory, while reducing Aβ 1−42 deposition and tau phosphorylation. +1 more finding

• Brain Biology
• Prevention

Scored 21 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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An astrocyte-neuron HSPB1 axis preserves lysosomal integrity and protects from tau pathology

16/100 ⚠ Preprint — not yet peer-reviewed Disease mechanisms Research Square

Key finding: Molecular chaperones are essential to prevent protein aggregation and, although typically studied as intracellular proteins, chaperones can also be secreted with functions that remain to be elucidated. +4 more findings

• Brain Biology

Scored 21 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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ALS-associated mutations reveal a conserved C-terminal self-assembly module in the TDP-43 low-complexity domain

16/100 ⚠ Preprint — not yet peer-reviewed Brain tissue and pathology bioRxiv

Key finding: TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein whose low-complexity domain (LCD) mediates self-assembly, liquid-liquid phase separation, and pathological aggregation associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). +1 more finding

• Brain Biology

Scored 27 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Upper cervical spinal cord morphometric charts: from population references to individualized clinical assessment

16/100 ⚠ Preprint — not yet peer-reviewed Vascular contributions medRxiv

Key finding: These deviation scores captured disease-specific abnormalities, enabled disease classification, and were associated with cognition, physical disability and disease progression. +1 more finding

• Other Dementias

Scored 31 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Social participation diversity and cognitive trajectories in older adults with hypertension and diabetes: a longitudinal cohort study

16/100 ⚠ Preprint — not yet peer-reviewed Prevention trials Research Square

Key finding: Greater diversity of social participation was associated with better long-term cognitive maintenance among older adults with hypertension and/or diabetes. +4 more findings

• Risk Factors

Scored 44 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Interpretable Frequency-Aware Deep Learning for Multi-Class EEG Classification of Neurological Disorders

16/100 ⚠ Preprint — not yet peer-reviewed Brain scans and imaging Preprints.org

Key finding: The model filters each EEG window into the delta, theta, alpha, beta, and gamma bands and processes every band in a separate convolutional branch with squeeze-and-excitation recalibration. +4 more findings

• Digital Tools

Scored 24 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Disease-Specific Perturbational Convergence Between Genetic-Risk and Disease-State Transcriptomic Signatures in Alzheimer's Disease

16/100 ⚠ Preprint — not yet peer-reviewed Genetics Research Square

Key finding: In the present analysis, genetic risk and end-stage AD pathology are largely decoupled at the level of individual genes and pathways but converge on a shared, pharmacologically modifiable response landscape.

• Genetics

Scored 31 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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A rapid, genetically-tractable human iPSC-derived model for studying tissue-resident macrophage biology in Alzheimer’s and other diseases

16/100 ⚠ Preprint — not yet peer-reviewed Genetics bioRxiv

Key finding: Robust TREM2 expression and signaling make iMacs a sensitive platform for interrogating TREM2 biology, with markedly higher phosphorylation of SYK and PLCγ2 in response to TREM2 engagement compared to iPSC-derived microglia. iMacs also tolerate lipid-mediated siRNA transfection with high survival and knockdown efficiency, enabling rapid genetic perturbation of AD risk genes.

• Genetics

Scored 21 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Mechanistic study of PHLDA1 in cognitive dysfunction of Alzheimer’s disease model mice via FoxO1‑mediated neuroinflammation

16/100 ⚠ Preprint — not yet peer-reviewed Biomarkers Research Square

Key finding: Collectively, the PHLDA1–FoxO1–TLR4 axis may significantly influence AD neuroinflammation, and targeting PHLDA1 provides a rationale for developing anti-inflammatory therapeutic strategies against AD.

• Brain Biology

Scored 21 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Symptom-Guided Blood Biomarker Testing for Alzheimer's Disease

59/100 ✓ Peer-reviewed Biomarkers Dementia and geriatric cognitive disorders

Key finding: Trial Parent study registrations: NCT01231971; NCT02854033. +1 more finding

• Biomarkers

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Electronic Health Record-Based Machine Learning Models for Predicting Revascularization, Amputation, and Cardiovascular Mortality in At-Risk Patients

16/100 ⚠ Preprint — not yet peer-reviewed Digital health tools Research Square

Key finding: Patients with peripheral artery disease (PAD), chronic limb-threatening ischemia (CLTI), and/or diabetic foot ulcer (DFU) are at increased risk for limb loss and death. +2 more findings

• Risk Factors
• Digital Tools

Scored 40 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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EEG Pathology Detection via Clinical Concept Bottleneck Models

16/100 ⚠ Preprint — not yet peer-reviewed Digital health tools bioRxiv

Key finding: Both CBMs approach the baseline on TUAB (82.7–82.9% vs 83.6%) and are 2–5 percentage points lower on CAUEEG (57.9–60.5% vs 62.7%). +4 more findings

• Digital Tools

Scored 24 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Subtype-Selective Neuronal Vulnerability and Compensatory Neuroglial Remodeling in Human Cortical Dementia

16/100 ⚠ Preprint — not yet peer-reviewed Disease mechanisms bioRxiv

Key finding: In DLPFC we observed alteration of mitochondrial and synaptic maintenance program in the pathological manifestation of disease. +4 more findings

• Brain Biology

Scored 21 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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α-Synuclein Seeding Activity in Fixed Antemortem Skin Biopsies From Patients With Synucleinopathies

16/100 ⚠ Preprint — not yet peer-reviewed Brain tissue and pathology Research Square

Key finding: Seeding readouts correlated with Hoehn and Yahr stage but not significantly with MoCA score or pS129 α-synuclein burden.

• Other Dementias

Scored 24 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Carbonaceous Components Underlying Wildfire Smoke PM 2.5 -Associated Alzheimer’s Disease and Related Dementias in Older US Adults

16/100 ⚠ Preprint — not yet peer-reviewed Risk factors medRxiv

Key finding: Per 1 µg/m 3 increase, smoke PM 2.5 was associated with incident AD (hazard ratio [HR], 1.015, 95% confidence interval [CI], 1.005-1.026) and ADRD (1.029 [1.024-1.035]). +3 more findings

• Risk Factors

Scored 24 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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The influence of cognitive decline on the severity and quantity of drug-drug interactions

16/100 ⚠ Preprint — not yet peer-reviewed Risk factors Research Square

Key finding: These findings indicate that cognitive impairment may mark a population vulnerable to medication complexity rather than independently driving DDI risk, with polypharmacy emerging as the principal modifiable determinant. +3 more findings

• Treatments

Scored 32 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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A large, comprehensive labeled MRI dataset of the human lateral ventricle choroid plexus

16/100 ⚠ Preprint — not yet peer-reviewed Brain scans and imaging bioRxiv

Key finding: However, limitation in the accuracy of the current segmentation tools highlight the need for more reliable methods to quantify ChP volume in healthy and clinical human populations. +4 more findings

• Brain Scans

Scored 21 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Continuous amyloid staging complements global amyloid burden in early Alzheimer’s disease

16/100 ⚠ Preprint — not yet peer-reviewed Brain scans and imaging bioRxiv

Key finding: A continuous amyloid staging score complements global amyloid burden for early AD staging and cognitive risk stratification. +1 more finding

Scored 35 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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DAP12-deficient microglia adopt a TREM2-independent antigen-presenting state with a glial-to-neuronal cascade in Nasu-Hakola disease

16/100 ⚠ Preprint — not yet peer-reviewed TREM2 and immune genetics bioRxiv

Key finding: TREM2-DAP12 is the switch that converts microglia from a surveillant to a reactive state; what DAP12-deficient microglia become and to what extent they reshape their microenvironment is unknown. +4 more findings

• Genetics
• Brain Biology

Scored 24 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Expression predictions inform molecular interpretation of Alzheimer’s disease risk loci

16/100 ⚠ Preprint — not yet peer-reviewed Genetics medRxiv

Key finding: Expression and splicing scores were associated with the corresponding Genotype-Tissue Expression (GTEx) quantitative trait locus (QTL) status, although these analyses did not establish colocalization or agreement in allelic direction. +1 more finding

• Genetics

Scored 21 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Mapping polygenic risk scores to brain cells: insights for neurodegenerative diseases

16/100 ⚠ Preprint — not yet peer-reviewed Genetics medRxiv

Key finding: We found substantial overlap among purportedly cell-type specific gene sets (21-29%), with APOE or neighbouring genes from the APOE locus represented in all gene sets, indicating that current cell-type specific annotations capture considerable shared genetic variation across cell-types. +1 more finding

• Genetics
• Brain Biology

Scored 21 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Clinical utility of plasma APOE proteotyping for Alzheimer’s disease risk and prognosis

16/100 ⚠ Preprint — not yet peer-reviewed Genetics medRxiv

Key finding: Plasma APOE4 proteotyping accurately distinguished genotype-defined APOE ε4 carrier status and copy number while demonstrating AD-related associations comparable to DNA genotyping.

• Genetics

Scored 32 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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Identifying Individualized Multiple Chronic Condition Pathways Associated with Dementia

16/100 ⚠ Preprint — not yet peer-reviewed Digital health tools Preprints.org

Key finding: Unlike traditional eager decision trees (eagerDT), which lacked sufficient training data for 17%-33% of patient profiles, lazyDT-MCCPath successfully modeled all profiles and achieved a 0.17 improvement in AUROC (0.66 vs. 0.83). lazyDT-MCCPath effectively translates pre-existing MCC profiles into personalized dementia risk probabilities for emerging conditions, which may help clinicians prioritize MCCs to monitor more closely.

Scored 21 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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ASC specks and α-synuclein amplify microglial NLRP3 inflammasome activation and co-localize with Lewy body pathology

16/100 ⚠ Preprint — not yet peer-reviewed Brain tissue and pathology bioRxiv

Key finding: Neuroinflammation is a hallmark of several chronic neurodegenerative disorders, including Parkinson’s disease (PD) and other synucleinopathies, and is closely associated with microglial activation. +4 more findings

• Brain Biology
• Other Dementias

Scored 21 on our rubric, shown as 16: non-peer-reviewed sources are capped at 16. See the breakdown.

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