JS PD KB

GBA-PD Biology

14 min read

GBA-PD Biology

Synthesis layer over the canonical by-photo corpus. This page does not replace data/processed/markdown/by-photo/. Every substantive statement links back to a source note or canonical transcription. Where the source carries Uncertain Spans, that uncertainty is preserved here rather than smoothed out.

Bounded synthesis. This page covers the 36 source pages that build Takeda’s integrative GBA / GD / GBA-PD biology block inside gba-pd-asyn (Pipeline of GD & GBA-PD > Summary / … > GBA / … > GD / … > GBA-PD). It is the biology-side companion of the GBA-PD pilot (gba-pd, gba-therapeutics, biomarkers) and α-synuclein topic (alpha-synuclein).

Overview

This page collects the corpus’s foundational GBA / GD / GBA-PD biology into one navigable synthesis. The 36 source pages run as one capture-time band on Page 144 / 197 / 200 / 261 of the source deck and sit between the GBA-PD pilot range (_181748–_181809) and the GBA / GCase modality cluster that follows (_182326–_182419). Reading order is four overlapping bands: a Takeda integrative **Summary chain

  • 총정리 GBA protein & activity** spine (Summary > 총정리 GBA protein & activity); a GBA biochemistry band (structure, BGL activity, catalytic pathway, glycosphingolipid substrates); a Gaucher Disease (GD) band (mutation classes, GD1 / GD2 / GD3 types and neuropathology, nGD animal models, oculomotor / retina nGD outcomes); and a GBA-PD band (GBA mutation in PD, MOA hypotheses, motor vs cognition, GBA-PD animal models, correction studies, GBA status vs UPDRS / MoCA). Cross-links to α-synuclein, GBA-PD pilot, and downstream GBA / GCase modality / supplement / biomarker clusters live in § Source Boundary / Delegation.

Authoring Rules

  • No domain-knowledge corrections. The page reflects what the sources record, not what the field is “supposed” to say.
  • Uncertain Spans on the source page are preserved as uncertainty; numeric values, mutation residue numbers, dose schedules, GBA-activity units, and Korean inline annotations are not paraphrased.
  • The body of data/processed/markdown/by-photo/ is not modified.
  • No raw photos are staged; no new figure assets added; figure-bearing pages are linked rather than re-embedded (docs/decisions/2026-04-29-body-purity-and-figure-only-embeds.md).
  • Tables on canonical pages are not re-quoted verbatim; the canonical link carries the table.
  • Out-of-scope sources (GBA / GCase modality cluster, α-synuclein, GBA-PD pilot, supplement anatomy chain, BioOrchestra biomarker cluster, brain-bank pages, TAK-071, PARKN GT) are linked, not re-narrated, per § Source Boundary / Delegation.

Source Boundary / Delegation

This topic is bounded against five sibling owners. Sources outside the 36-page set are linked from this section, not re-narrated in the axis sections.

neighbour clusterstemsowner
GBA-PD pilot range20240722_181748–20240722_181809 (6 pages)gba-pd, gba-therapeutics, biomarkers, eliglustat, ambroxol, venglustat, pr001
α-synuclein Tier 1 (incl. _182149 a-syn POSTMORTEM interleaved in the Summary chain)per alpha-synuclein-source-boundaryalpha-synuclein
GBA / GCase modality cluster (PET Imaging GBA, GBA Activator, GBA GT, RD-DDU, GALC, KD pipeline, etc.)20240722_182326, _182330, _182333–_182419future Cluster B synthesis (not yet created)
TAK-071 program20240722_181839tak-341 sibling backlog (TAK-071 backlog row on therapeutic-programs)
PARKN GT cross-filed page20240722_182103parkn-gt
Supplement anatomy chain20240722_182422–_182447section-only (see gba-pd-asyn)
BioOrchestra biomarker catalog (Cluster C)20240722_182708–_183115 (74 stems; _183050 excluded as α-synuclein Tier 1)bioorchestra-biomarker-catalog
Brain Bank head and standalone Brain Bank (Cluster D)20240722_182617–_182704; _184200, _184203brain-banks-postmortem

topics/alpha-synuclein.md is not modified in this pass. Cluster A pointer cleanup can happen later as a small separate pass.

Source Coverage

All 36 sources share the same first nav_path entry; the cluster collapses into a single nav-root row with a four-axis split below.

nav root (first nav_path entry)sourcescovered axis
Pipeline of GD & GBA-PD36Summary / 총정리 GBA protein & activity (10) · GBA biochemistry (6) · GD biology (11) · GBA-PD biology (9)
total36

Across these 36 sources, the source-note frontmatter records 104 uncertain_span_count entries and 2 body-embedded figure assets — review surface area, not resolutions. Both embedded figures sit on 20240722_181813 (the PR001A clinical-trial bridge that opens the Summary chain) and remain at the canonical by-photo level per the 2026-04-29 body-purity decision.

Summary / 총정리 GBA Protein & Activity Chain

Ten pages form Takeda’s integrative summary spine. They run from the PR001A clinical-trial / GBA-PD trial-comparison bridge that closes the GBA-PD pilot, through the Page 144 총정리 GBA protein & activity matrix block, and into the Page 197 Summary > GBA Sidransky-2012 review continuation that hands off into the GBA biochemistry band. The Summary axis is the cross-cutting reading-order spine of this topic, and three pages here interleave with sibling axes:

  • Pipeline of GD & GBA-PD > Summary (PR001A / GBA-PD trial comparison bridge). PR001A PROPEL / PROVIDE / PROGRESS / PROCEED blocks, Study Objectives And Endpoints, the GBA-PD Clinical Trial Comparison Table, the Miglustat clinical-trial row, S-181 preclinical evidence, and the NCGC607 entry sit on (md). Two body-embedded figure assets and three Uncertain Spans are recorded; PR001 program detail is owned by pr001, miglustat / S-181 / NCGC607 detail is delegated to gba-therapeutics § Strategy Map. Linked here, not re-narrated.
  • Pipeline of GD & GBA-PD > Summary (Synapse / postmortem matrix / PD-GD stratification). Synapse, the 총정리 GBA protein & activity POSTMORTEM matrix opener, the PD only / PD+ heteroz / Hetero only / GD only / PD+GD patient-stratification matrix, and Peripheral blood / GD studies sit on (md). Five Uncertain Spans recorded.
  • Summary > 총정리 GBA protein & activity chain. Five capture-time-adjacent pages walk the integrative GBA-protein-and- activity-vs-postmortem matrix (md, md, md, md) plus two sub-headings: Summary GBA protein & activity, GlcCer, GlcSph (md) and Summary GBA protein & activity (md). Per-page Uncertain Spans run 3–9 (page-141 hot spot _182133 carries 9 uncertain entries — image-primary postmortem cell values; re-check the canonical page rather than this topic).
  • Summary > 총정리 GBA protein & activity > Read the Paper. A paper-pointer page held inside the Summary block (md, 7 uncertain spans).
  • Summary > GBA (Sidransky 2012 review continuation). The Page 197 hand-off page picks up the Sidransky 2012 review-table continuation, the PD-GD / GBA1-PD notes block, an inline GBA status header, and the GBA Mutation detection method survey. It bridges the Summary spine into the GBA biochemistry band that opens on the next page (md, 5 uncertain spans).

The α-synuclein POSTMORTEM page (20240722_182149) sits between _182146 and _182153 in capture order and is interleaved into the same 총정리 GBA protein & activity Summary chain in the source deck. It is delegated to alpha-synuclein § Postmortem and Lewy Pathology and is not included in this topic’s Source Table; readers walking the Summary chain in capture order should open it on the α-synuclein page.

GBA Biochemistry — Structure, BGL Activity, Catalytic Pathway, Substrates

Six pages cover the protein-and-activity foundation under Pipeline of GD & GBA-PD > GBA. Reading-order anchors:

  • Structure of GBA protein. GBA protein structure, function, turnover, expression, lifecycle, and the lead-in to the BGL activity test (md, 0 uncertain spans). Includes the carrier-screening continuation from the preceding Summary > GBA page.
  • BGL activity test. GBA activity (BGL test) block — the catalytic-activity assay anchor for the GBA-PD pipeline (md, 3 uncertain spans).
  • Catalytic pathway. The GBA-substrate catalytic pathway opener (md) and two adjacent Gangliosides pages (md, md).
  • Glycosphingolipid substrates — GlcCer / GlcSph / gangliosides. The GlcSph leaf under Catalytic pathway > Gangliosides > GlcSph (md, 2 uncertain spans). GlcCer / GlcSph also appear as biomarker readouts on the GBA-PD pilot biomarker matrix (biomarkers Seed Biomarker Set), which is linked rather than re-narrated.

Gaucher Disease (GD) Biology — Mutation, Type, nGD Animal Model, Oculomotor / Retina

Eleven pages cover Gaucher Disease itself under Pipeline of GD & GBA-PD > GD. Reading-order anchors:

  • Mutations Summary. GD diagnosis (Dx), epidemiology / prevalence, the Mutations Summary block, the GBA mutation distribution figure text labels, prevalence of GBA mutation in GD, and the Pathophysiology In GD opener (md, 3 uncertain spans).
  • Types and Neuropathology — GD1 / GD2 / GD3. The GD-type and neuropathology overview (md, 2 uncertain spans). Per-type detail is split across:
    • GD 1 Summary (md, 2 uncertain spans).
    • GD 3 Summary — two adjacent pages (md, md; 5 / 4 uncertain spans).
  • Animal models of GD (nGD). Three pages walk the nGD animal-model inventory: an opener that includes the 2019 Lukina Eliglustat re-shown block and the GCB mouse-model substrate comparison (md); a continuation page including the D409V hetero opener (md); and the nGD outcome-measure leaf at Animal models of GD > Outcome measure in nGD (md).
  • Oculomotor and retina parameters in nGD. Three pages cover the nGD ophthalmologic outcome axis under GD > Parameters: two Oculomotor measurements pages (md, md) and the Retina in nGD page (md, 0 uncertain spans).

GBA-PD Biology — GBA Mutation in PD, MOA, Motor vs Cognition, Animal Models, Correction, GBA Status vs UPDRS / MoCA

Nine pages cover GBA-PD itself under Pipeline of GD & GBA-PD > GBA-PD. Reading-order anchors:

  • Mutation GBA-PD. Penetrance (LIFETIME), the Mutation GBA-PD classification block (Severe, Mild, Other risk variant subheadings), and the three-most-common-variant ranking sit here, alongside the WORLDSymposium 2021 Ayuko Iverson and Narita Aya (Tottori) reading-order entries and the Handover to Otake on GD operations note that closes the GD band (md, 2 uncertain spans).
  • MOA GBA-PD. Postmortem GBA-PD continuation, odds ratios, Phenotype of GBA-PD, Cognition GBA-PD, the gene-dose-effect-in-PD block, and the MOA GBA-PD opener (md, 2 uncertain spans).
  • Motor vs Cognition. aSyn spreading continuation, ER stress, OS, Inflammation, Motor vs Cognition split, the PD / MCI / Dementia cognition matrix, and the GBA-PD / Phenotypes (assays) / Models / Status / Current/future plan opener (md, 1 uncertain span). The aSyn-spreading half of this page is delegated to alpha-synuclein (cross-link only).
  • Animal models of GBA-PD. (md, 0 uncertain spans).
  • Correction studies. Two adjacent pages walk the GBA-PD correction-study evidence: the A53T α-syn animal-model continuation and the Sardi 2018 row (md), and the S15 model comparison continuation (md; 1 / 1 uncertain spans).
  • GBA status vs UPDRS vs MoCA. Three pages walk the GBA-PD patient-selection / clinical-development scenario grid (Patient Selection, nGD biomarker / study-design grid, Model, Omics / Imaging / Neurophysiologic / CSF proteomics, Resources / BMx Milestones, Patient-recruitment feasibility, Already genotyped vs Screening, GBA vs UPDRS vs MOCA, Clinical-dev Scenarios) (md, md, md; 3 / 1 / 0 uncertain spans). Clinical-scale and patient-stratification detail is also referenced from biomarkers-outcomes (UPDRS / MoCA axes), which is linked rather than re-narrated.

Source Table

Provenance ground-truth for the 36 sources, in capture-time order.

stemnav path / headingsource notecanonicaluncertain spansembedded images
20240722_181813Pipeline of GD & GBA-PD > Summarynotemd32
20240722_182123Pipeline of GD & GBA-PD > Summarynotemd50
20240722_182126Pipeline of GD & GBA-PD > Summary > 총정리 GBA protein & activitynotemd70
20240722_182130Pipeline of GD & GBA-PD > Summary > 총정리 GBA protein & activitynotemd50
20240722_182133Pipeline of GD & GBA-PD > Summary > 총정리 GBA protein & activitynotemd90
20240722_182136Pipeline of GD & GBA-PD > Summary > 총정리 GBA protein & activity > Summary GBA protein & activity, GlcCer, GlcSphnotemd30
20240722_182139Pipeline of GD & GBA-PD > Summary > 총정리 GBA protein & activity > Summary GBA protein & activitynotemd70
20240722_182143Pipeline of GD & GBA-PD > Summary > 총정리 GBA protein & activity > Read the Papernotemd70
20240722_182146Pipeline of GD & GBA-PD > Summary > 총정리 GBA protein & activitynotemd60
20240722_182153Pipeline of GD & GBA-PD > Summary > GBAnotemd50
20240722_182157Pipeline of GD & GBA-PD > GBA > Structure of GBA proteinnotemd00
20240722_182200Pipeline of GD & GBA-PD > GBA > GBA activity (BGL test)notemd30
20240722_182203Pipeline of GD & GBA-PD > GBA > Catalytic pathwaynotemd10
20240722_182207Pipeline of GD & GBA-PD > GBA > Catalytic pathway > Gangliosidesnotemd20
20240722_182210Pipeline of GD & GBA-PD > GBA > Catalytic pathway > Gangliosidesnotemd50
20240722_182213Pipeline of GD & GBA-PD > GBA > Catalytic pathway > Gangliosides > GlcSphnotemd20
20240722_182216Pipeline of GD & GBA-PD > GD > Mutations Summarynotemd30
20240722_182219Pipeline of GD & GBA-PD > GD > Types and Neuropathologynotemd20
20240722_182224Pipeline of GD & GBA-PD > GD > Parameters > GD 1 Summarynotemd20
20240722_182227Pipeline of GD & GBA-PD > GD > Parameters > GD 3 Summarynotemd50
20240722_182230Pipeline of GD & GBA-PD > GD > Parameters > GD 3 Summarynotemd40
20240722_182233Pipeline of GD & GBA-PD > GD > Animal models of GDnotemd10
20240722_182237Pipeline of GD & GBA-PD > GD > Animal models of GDnotemd20
20240722_182241Pipeline of GD & GBA-PD > GD > Animal models of GD > Outcome measure in nGDnotemd20
20240722_182245Pipeline of GD & GBA-PD > GD > Parameters > Oculomotor measurementsnotemd10
20240722_182248Pipeline of GD & GBA-PD > GD > Parameters > Retina in nGDnotemd00
20240722_182252Pipeline of GD & GBA-PD > GD > Parameters > Oculomotor measurementsnotemd10
20240722_182255Pipeline of GD & GBA-PD > GBA-PD > Mutation GBA-PDnotemd20
20240722_182259Pipeline of GD & GBA-PD > GBA-PD > MOA GBA-PDnotemd20
20240722_182303Pipeline of GD & GBA-PD > GBA-PD > Motor vs Cognitionnotemd10
20240722_182306Pipeline of GD & GBA-PD > GBA-PD > Animal models of GBA-PDnotemd00
20240722_182310Pipeline of GD & GBA-PD > GBA-PD > Correction studiesnotemd10
20240722_182313Pipeline of GD & GBA-PD > GBA-PD > Correction studiesnotemd10
20240722_182316Pipeline of GD & GBA-PD > GBA-PD > GBA vs UPDRS vs MOCAnotemd30
20240722_182320Pipeline of GD & GBA-PD > GBA-PD > GBA vs UPDRS vs MOCAnotemd10
20240722_182323Pipeline of GD & GBA-PD > GBA-PD > GBA vs UPDRS vs MOCAnotemd00

Totals across the 36 sources: uncertain_span_count = 104; embedded_image_count = 2. Per-axis subtotals:

  • Summary chain (10 pages): 57 uncertain spans, 2 embedded images.
  • GBA biochemistry (6 pages): 13 uncertain spans, 0 embedded images.
  • GD biology (11 pages): 23 uncertain spans, 0 embedded images.
  • GBA-PD biology (9 pages): 11 uncertain spans, 0 embedded images.

Numbers are review surface area, not resolutions.

Uncertainties Carried Forward

Uncertainty hot spots worth checking before any downstream extraction. The page does not paraphrase the uncertain content; open the canonical page for cell values.

  • 총정리 GBA protein & activity matrix density (_182133 9 uncertain spans; _182126, _182139, _182143 7 each; _182146 6; _182130 5). The Page 144 postmortem-and-activity matrix block carries the largest uncertainty surface in the topic — re-check these canonical pages rather than acting on summarised cell values.
  • Sidransky 2012 review continuation (_182153, 5 uncertain spans). The Summary > GBA hand-off page from the Summary spine into the GBA biochemistry band carries Sidransky-2012-table cell values that warrant a canonical re-check.
  • PR001A clinical-trial bridge (_181813, 3 uncertain spans, 2 body-embedded figures). Trial endpoints, the GBA-PD Clinical Trial Comparison Table, the Miglustat clinical-trial row, and the S-181 / NCGC607 entries hand off to pr001 and gba-therapeutics; the embedded figure assets remain at the canonical level.
  • Synapse / postmortem matrix opener (_182123, 5 uncertain spans). The PD only / PD+ heteroz / Hetero only / GD only / PD+GD patient-stratification matrix and the Peripheral-blood / GD-studies block sit on this page.
  • GD3 parameters (_182227 5, _182230 4 uncertain spans). The GD type-3 axis carries the highest uncertainty count inside the GD biology band.
  • Catalytic pathway / Gangliosides (_182210, 5 uncertain spans). The mid-Gangliosides page is the densest within the GBA biochemistry band.
  • GBA mutation distribution figure labels (_182216, 3 uncertain spans). The figure labels for the GBA-mutation distribution figure are reproduced as text on the canonical page; re-check there for residue numbers and frequency values.
  • GBA-PD patient-selection / clinical-dev scenarios (_182316, 3 uncertain spans). The Patient Selection / nGD biomarker grid / Patient-recruitment feasibility / Clinical-dev Scenarios block carries inline scenario labels that warrant a canonical re-check.
  • Read the Paper pointer page (_182143, 7 uncertain spans). A paper-pointer page held inside the Summary block; uncertainty is in citation labels rather than data cells.
  • α-synuclein POSTMORTEM interleave (20240722_182149, not in this topic’s Source Table). This page sits between _182146 and _182153 in capture order and is interleaved into the same Summary chain; it is owned by alpha-synuclein § Postmortem and Lewy Pathology. Readers walking the Summary chain in capture order should open it on the α-synuclein page; uncertainty on _182149 is preserved there.

그래프 뷰

백링크