Ahmed Negida, MBBCh, PhD

Ahmed Negida, MBBCh, PhD MBBCh, Ph.D.
★ Physician-Scientist
★ Founder & Co-PI of GNC research collaborative

Ozkaya et al. review the brain-gut axis in PD pathology in Comprehensive Physiology. The Braak hypothesis — that alpha-s...
04/12/2026

Ozkaya et al. review the brain-gut axis in PD pathology in Comprehensive Physiology. The Braak hypothesis — that alpha-synuclein pathology may originate in the gut and propagate to the brain via the vagus nerve — has gained substantial support. This review synthesizes evidence from vagotomy studies, microbiome research, and enteric pathology. GI symptoms may be among the earliest identifiable signs of prodromal PD.

https://doi.org/10.1002/cph4.70137

This paper addresses something that has been quietly bothering the clinical trials field: co-occurring neuropathologies....
04/10/2026

This paper addresses something that has been quietly bothering the clinical trials field: co-occurring neuropathologies. In 6,424 autopsy-confirmed cases, over a third harbored two or more proteinopathies. Each additional pathology accelerated cognitive decline by 0.25 CDR-SB points per year. The most striking finding: TDP-43 copathology added roughly 1.5 CDR-SB points over 18 months — that exceeds the treatment effect of lecanemab. If we are running AD trials without accounting for TDP-43 or Lewy copathology, we are introducing a confounder that could mask or exaggerate treatment effects. Biomarker-based stratification for copathologies should become standard.

https://www.researchsquare.com/article/rs-9188042/v1

Which autonomic symptoms actually predict cognitive decline in PD? This paper takes an item-level approach to the SCOPA-...
04/09/2026

Which autonomic symptoms actually predict cognitive decline in PD? This paper takes an item-level approach to the SCOPA-AUT in 960 PPMI patients and identifies 8 specific symptoms across gastrointestinal, urinary, cardiovascular, and thermoregulatory domains that independently predict cognitive milestones. The dose-response relationship — more affected domains, earlier decline — supports the idea that widespread autonomic failure reflects more diffuse alpha-synuclein pathology. Practically, this means a careful autonomic history at baseline could help stratify PD patients for cognitive prognosis.

https://www.researchsquare.com/article/rs-9129721/v1

PD heterogeneity is one of the biggest challenges in designing disease-modification trials. If your trial mixes slow and...
04/08/2026

PD heterogeneity is one of the biggest challenges in designing disease-modification trials. If your trial mixes slow and rapid progressors, you dilute the signal and risk a false-negative result. This paper follows PD patients for 10 years, comparing how clinical subtypes (tremor-dominant vs PIGD), pathological subtypes, and data-driven subtypes differ in reaching key progression milestones. The practical question is: which subtyping framework best identifies the patients most likely to progress? Critical reading for anyone involved in PD trial design.

https://doi.org/10.21203/rs.3.rs-6574563/v1

Cholinesterase inhibitors remain the recommended first-line symptomatic treatment for DLB — the evidence for cognitive b...
04/08/2026

Cholinesterase inhibitors remain the recommended first-line symptomatic treatment for DLB — the evidence for cognitive benefit is arguably stronger than in AD. Yet surprisingly little is known about how ChEIs are actually prescribed in DLB in the real world. This paper examines prescribing patterns and predictors of ChEI use specifically in DLB patients. Understanding the gap between guideline recommendations and clinical practice is the first step toward closing it. Particularly relevant as we enter an era of anti-amyloid therapies that may not benefit DLB patients the same way.

https://doi.org/10.1002/trc2.70136

There has been a lot of interest in subtyping PD-MCI beyond the traditional cognitive domain approach. This paper explor...
04/06/2026

There has been a lot of interest in subtyping PD-MCI beyond the traditional cognitive domain approach. This paper explores whether MRI evidence of cholinergic nucleus 4 (basal forebrain) degeneration can define a distinct PD-MCI subtype. The rationale is solid — Ch4 is the primary source of cortical acetylcholine, and its degeneration correlates with both cognitive decline and response to ChEIs. If we can identify these patients early through structural imaging, it opens the door to more targeted cholinergic therapy rather than a one-size-fits-all approach. Worth reading for anyone thinking about precision medicine in PD.

https://doi.org/10.1016/j.parkreldis.2025.108072

One of the things that keeps coming up in clinical practice is how unevenly cholinesterase inhibitors get prescribed acr...
04/06/2026

One of the things that keeps coming up in clinical practice is how unevenly cholinesterase inhibitors get prescribed across dementia subtypes. This paper looked at 3,166 patients with AD, DLB, and VaD and found some striking patterns. DLB patients had the highest ChEI fill rates both before and after diagnosis, which makes sense given the cholinergic deficit profile. But the real finding here is the disparity: after adjusting for demographics, women were 19% less likely and ethnoracially minoritized patients 26% less likely to fill a ChEI prescription. We talk a lot about health equity in neurodegeneration — this is exactly the kind of data we need to quantify the problem.

https://doi.org/10.1177/13872877251411418

04/05/2026

Early motor deficits, sleep dysfunction, and selective dopaminergic neuron loss in a PARK7 (DJ-1) knockout model reported in Scientific Reports. DJ-1 mutations cause early-onset PD, and this model recapitulates key prodromal features — sleep disruption preceding motor symptoms. Understanding the temporal sequence of pathology is crucial for identifying therapeutic windows.

https://doi.org/10.1038/s41598-026-39692-0

López-Martos and colleagues dive into the longitudinal relationship between early-changing AD biomarkers and cognitive t...
04/03/2026

López-Martos and colleagues dive into the longitudinal relationship between early-changing AD biomarkers and cognitive trajectories—and the nuance here is important. Not all biomarker positivity predicts equivalent cognitive decline; the *combination* of multimodal markers tells a richer story.

What strikes me is how they map this across preclinical disease. We've been collecting amyloid and tau biomarkers for years, but understanding which combination best predicts who will actually progress cognitively is what changes clinical practice. This is the bridge between research biomarkers and individual risk stratification.

Why this matters for the clinic: We're moving away from single-marker thinking toward integrated prediction models that could guide counseling and intervention timing.

https://doi.org/10.1212/WNL.0000000000214308

Cullinane, Yang, and Chelban identify frontotemporal dementia with MSA-type α-synuclein pathology (FTLD-synuclein) and c...
04/03/2026

Cullinane, Yang, and Chelban identify frontotemporal dementia with MSA-type α-synuclein pathology (FTLD-synuclein) and characterize its seeding properties and cryo-EM filament structure alongside typical MSA. This is careful nosological and mechanistic work at the synucleinopathy intersection.

What's particularly revealing is that FTLD-synuclein shows identical seeding and structural features to typical MSA, despite different clinical presentations. This suggests a shared pathogenic α-synuclein strain circulating across phenotypically distinct diseases—a key concept in prion-like spreading.

Clinically, this complicates but also clarifies our thinking: Synuclein conformation, not just regional distribution, determines disease expression. Understanding strain differences could eventually guide phenotype-specific therapeutics targeting specific oligomeric forms.

https://doi.org/10.1111/nan.70013

A comprehensive scoping review in Molecular Neurodegeneration mapping systems biology pathways in Alzheimer's disease. R...
04/02/2026

A comprehensive scoping review in Molecular Neurodegeneration mapping systems biology pathways in Alzheimer's disease. Rather than studying individual genes or proteins in isolation, this review synthesizes network-level interactions across amyloid, tau, neuroinflammation, and metabolism. Essential reading for understanding where the field's therapeutic targets intersect.

https://doi.org/10.1186/s13024-026-00934-4

Wang et al. in Scientific Reports use Mendelian randomization to examine CSF and plasma metabolites associated with Park...
04/02/2026

Wang et al. in Scientific Reports use Mendelian randomization to examine CSF and plasma metabolites associated with Parkinson's disease. MR studies provide a way to infer causal relationships from observational data — identifying metabolites that are causally linked to PD risk opens new avenues for biomarker development and therapeutic targets.

https://doi.org/10.1038/s41598-025-30521-4

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