| Domain | Test or intervention | Purpose | Notes | Suggested ontology term(s) | Evidence/citation IDs |
|---|---|---|---|---|---|
| genetic | Targeted **ITM2B/BRI2** testing for the Danish duplication (**c.787_796dupTTTAATTTGT**, p.Ser266PhefsTer11 / p.Ser266PhefsX11) | Confirm molecular diagnosis in symptomatic individuals and enable family testing | Core disease-defining test; the mutation is an autosomal dominant 10-nt duplication near the stop codon that generates the 277-aa precursor processed to ADan | Ontology: not assigned | (pqac-00000001, pqac-00000004, pqac-00000003) |
| diagnostic | Family-history assessment and pedigree analysis | Identify at-risk relatives and support suspicion of autosomal dominant inherited amyloidosis | Especially useful because published human disease derives from a multigenerational Danish pedigree/case series | Ontology: not assigned | (pqac-00000004, pqac-00000003) |
| imaging | Brain neuroimaging (reported findings: ventricular dilatation, periventricular white-matter changes) | Support clinical workup and assess CNS structural involvement | Imaging findings are nonspecific but compatible with disease burden; no disease-specific imaging guideline retrieved | Ontology: not assigned | (pqac-00000004) |
| pathology | Neuropathologic examination of brain/retina/vessels for **ADan amyloid** and **CAA** | Establish tissue-level diagnosis and characterize disease severity/distribution | Hallmarks include widespread cerebral and retinal amyloid angiopathy, predominantly vascular deposits, and often absence of compact parenchymal plaques | SNOMED/LOINC: not assigned | (pqac-00000001, pqac-00000004, pqac-00000006) |
| pathology | Histochemistry for amyloid (e.g., Congo red / thioflavin-based methods in reported studies) | Detect amyloid deposition in tissue | Some FDD hippocampal deposits were reported Congo red/ThS negative in certain reports, so interpretation depends on lesion type/stage | SNOMED/LOINC: not assigned | (pqac-00000001, pqac-00000004) |
| pathology | Assessment for **tau pathology / neurofibrillary tangles** | Document Alzheimer-like downstream neurodegeneration | Hippocampal neurofibrillary tangles and paired helical filaments are recurrent pathologic features | SNOMED/LOINC: not assigned | (pqac-00000001, pqac-00000003, pqac-00000004) |
| diagnostic | Ophthalmologic evaluation (including cataract assessment) | Detect early disease manifestations and functional impairment | Visual symptoms are often the first manifestation, with median onset around 27 years in one family series | Ontology: not assigned | (pqac-00000001, pqac-00000004) |
| diagnostic | Audiologic evaluation | Characterize progressive hearing loss and disability burden | Hearing loss typically follows ocular disease by 10–20 years and may be severe by the fifth decade | Ontology: not assigned | (pqac-00000001, pqac-00000004) |
| diagnostic | Neurologic and cognitive assessment | Monitor progression of ataxia, tremor, gait dysfunction, and dementia | Important for longitudinal care; no standardized disease-specific criteria retrieved | Ontology: not assigned | (pqac-00000001, pqac-00000002, pqac-00000004, pqac-00000006) |
| supportive | Symptomatic multidisciplinary care (neurology, ophthalmology, audiology, rehabilitation, dementia care) | Maintain function and quality of life | No disease-modifying approved therapy was retrieved; current care is supportive and complication-focused | MAXO: supportive care procedure; rehabilitation intervention; dementia management (specific term not assigned) | (pqac-00000001, pqac-00000004, pqac-00000006) |
| supportive | Physical therapy / gait and balance rehabilitation | Address ataxia, gait abnormality, and motor dysfunction | Supported by the prominence of cerebellar ataxia and progressive motor impairment; evidence is extrapolated from phenotype, not trial-based | MAXO: physical therapy | (pqac-00000002, pqac-00000004, pqac-00000028) |
| supportive | Hearing and vision support | Mitigate sensory disability from deafness and cataracts | Includes standard-of-care assistive and ophthalmologic management; disease-specific outcomes data not retrieved | MAXO: assistive device intervention / ophthalmologic management (not assigned) | (pqac-00000001, pqac-00000004) |
| experimental-preclinical | Anti-ADan monoclonal antibody **1B7** | Neutralize ADan-mediated cytotoxicity | In SH-SY5Y experiments, 1B7 completely neutralized ADan-mediated toxicity, supporting target-specific anti-amyloid strategies | MAXO: monoclonal antibody therapy (preclinical) | (pqac-00000017, pqac-00000020) |
| experimental-preclinical | Antioxidant **Trolox** | Reduce ADan-triggered oxidative stress and downstream apoptosis | Preclinical cell data show Trolox reduced ROS-linked caspase-3 activation, supporting oxidative-stress targeting | MAXO: antioxidant therapy (preclinical) | (pqac-00000018, pqac-00000019, pqac-00000020, pqac-00000033) |
| experimental-preclinical | APP-lowering genetic modification (APP haplodeficiency in KI models) | Test whether APP-derived products mediate synaptic/memory deficits | In FDD models, APP reduction prevented synaptic plasticity and memory deficits, arguing that APP metabolites are mechanistically important | MAXO: gene dosage reduction / genetic interaction study (preclinical) | (pqac-00000007, pqac-00000030) |
| experimental-preclinical | Targeting microglial **BRI2-TREM2** biology | Explore disease-modifying approaches via microglial processing/phagocytosis pathways | 2024 studies implicate microglial ITM2B enrichment, altered TREM2 processing, and reduced phagocytosis after BRI2 loss; therapeutic relevance remains investigational | MAXO: targeted molecular therapy (preclinical) | (pqac-00000009, pqac-00000014, pqac-00000015) |
| experimental-preclinical | Clinical trials search for ADan/FDD-specific interventions | Assess real-world translational pipeline | No ADan/FDD-specific interventional trials were retrieved in the current tool context | Ontology: not assigned | (pqac-00000000) |


*Table: This table summarizes currently supported diagnostic approaches, pathology findings, supportive care practices, and preclinical therapeutic leads for ADan amyloidosis/familial Danish dementia. It is useful for distinguishing established clinical implementation from experimental mechanisms-based interventions.*