January 2026 Research Update

This month added a focused look at what happens when ATTR amyloid builds up years after a domino liver transplant, and how disease-modifying drugs performed in that situation. In this group, amyloid deposits were often detected several years after transplant, and tafamidis was linked with stable neuropathy symptoms for many people, even when nerve testing continued to show silent (subclinical) worsening. A small number had meaningful symptom progression during tafamidis that appeared to settle after switching to an siRNA therapy. [1]

The study followed 30 transplant recipients and reported amyloid deposition in 17 people at a median of 7.7 years after transplant. Among those followed more than 3 years after amyloid was detected, most were described as clinically stable on tafamidis, while nerve conduction studies still showed ongoing axonal damage that might not be obvious day to day. Only one person developed clinically significant heart amyloid in this series. [1]

For patients and caregivers, this mainly matters for people who received a domino liver transplant from an ATTRv donor and are being followed long term. It adds a clearer picture that symptoms and test results may not always move in the same direction, because nerve tests can change even when day-to-day neuropathy feels stable. The evidence here comes from one center's retrospective experience, so it does not tell what will happen for every person or which medicine is best, but it helps set expectations for the kinds of changes that can be tracked over years in this unique situation. [1]

This month, studies looking at testing in ATTRv polyneuropathy pointed in a similar direction: subtle nervous system changes can be measured even before obvious symptoms, but dramatic brain findings were not common. A pain-nerve test detected differences in both symptomatic patients and presymptomatic carriers compared with healthy controls. Brain MRI work found diffuse changes in the brain's wiring (white matter) and mild thinking changes that were more noticeable in symptomatic people, without clear evidence of widespread thinning of the brain surface. [2] [3]

One study tested pain-related evoked potentials (a way to measure how small pain-sensing nerves carry signals) in the hands and feet. Both ATTRv-PN patients and presymptomatic carriers had longer signal timing and smaller signal size than controls, especially in the legs, which the authors interpreted as small-fiber involvement. Because the groups were small, this work is best read as an early signal that this kind of test could be useful for tracking nerve involvement. [2]

A separate study combined cognitive testing with several MRI approaches in symptomatic ATTRv-PN, presymptomatic carriers, and controls. It reported widespread white matter microstructural changes on diffusion imaging in symptomatic ATTRv-PN, along with lower memory and verbal fluency scores compared with presymptomatic carriers, while cortical thinning was not seen. Microbleeds were infrequent in this cohort, and links between MRI measures and clinical severity were not strong after accounting for multiple comparisons. [3]

For patients, this set of studies mainly adds understanding of what testing can pick up in the nervous system, rather than changing what anyone should do now. It suggests that some specialized tests may detect early or subtle nerve and brain involvement, including in some presymptomatic carriers, which could matter in the future if these tools are validated for monitoring. What remains uncertain is how well these test changes predict day-to-day symptoms or future progression, because the studies were cross-sectional snapshots and involved modest numbers of people. [2] [3]

This month strengthened the picture that ATTRv is not one uniform condition: when symptoms begin and how the disease is noticed can differ widely depending on the specific TTR variant and a person's background. A Brazilian cohort showed large differences in age of onset across variants and regions, and earlier diagnosis in families already under presymptomatic monitoring. In parallel, a health-system study developed a phenotype risk score that better highlighted likely V142I carriers in electronic records than a generic approach, aiming to reduce missed opportunities for genetic testing. [4] [5]

In 175 Brazilian patients from 45 families, seven TTR variants were identified, most commonly V30M and V142I, with different typical ages of onset across variants. The study also reported that having a family history was linked with earlier onset, and that people enrolled in presymptomatic monitoring were diagnosed at a younger age than those not monitored. Place of birth showed a strong relationship with age of onset in the V30M subgroup, highlighting how the same variant can look different across communities. [4]

Using Mount Sinai's BioMe biobank, researchers built a customized phenotype risk score for the V142I variant using expert-chosen health record features, and it more precisely prioritized likely carriers than a standard coding-based score. The improvement was most noticeable among older African American individuals with heart failure, where the top-scoring group included more V142I carriers than expected by random sampling. The authors described this as a potential way for health systems to target genetic testing more efficiently, while noting limits from coding gaps and differences between health systems. [5]

Another study addressed a common diagnostic confusion in neuropathy: nerve conduction slowing that can resemble CIDP (a treatable inflammatory neuropathy). Comparing 96 V30M ATTRv patients with 175 people who had nutritional or alcohol-related axonal neuropathy, the researchers found that CIDP-like slowing occurred mainly in those with severe axonal loss, suggesting the slowing often reflects nerve fiber loss rather than primary demyelination. After adjusting for factors like age and nerve signal size, more pronounced slowing remained mainly in the median nerve, leaving open whether additional mechanisms contribute there. [6]

For patients and caregivers, these studies help explain why ATTRv can be diagnosed earlier in some families and later in others, and why doctors may use different clues depending on the variant and setting. The cohort data support that variant type, family history, and local background can shape when symptoms start and when diagnosis happens, which may matter for planning long-term follow-up and family discussions, even though the study cannot separate biology from referral patterns. The risk-score work is mainly health-system research for now, but it points toward future approaches that could flag people at higher likelihood of carrying V142I using routine records. The nerve-conduction comparison helps clarify that certain nerve test patterns can occur as nerves are lost over time, which may reduce misinterpretation, but it does not by itself determine an individual's diagnosis. [4] [5] [6]

This month included two case reports that underline how ATTRv can present in very different ways, including prominent autonomic symptoms and rare brain-and-eye involvement. It also included early laboratory work suggesting a natural compound can disrupt already-formed TTR amyloid fibrils, a different idea from drugs that stabilize TTR. Together, these reports broaden understanding and generate hypotheses, but they do not show what will happen for most patients. [7] [8] [9]

One case described a woman with the p.Asp58Val variant who had autonomic neuropathy, polyneuropathy, and cardiomyopathy, with improved postural symptoms and quality of life over 12 months during multidisciplinary management, though she did not return to her prior baseline. The report noted that epigallocatechin-3-gallate (EGCG) caused excessive sweating and was stopped, while doxycycline and diflunisal were described as well tolerated. Because this is a single patient and included multiple simultaneous management steps, it cannot show which elements drove the changes. [7]

A second case reported oculoleptomeningeal amyloidosis due to the p.Arg54Gly variant, with imaging and biopsy evidence of leptomeningeal and systemic amyloid. The patient had ongoing neurologic episodes despite tafamidis, and the report expanded the described symptom range to include events such as seizures alongside brain imaging changes. As with any single case, it primarily signals what can occur rather than how common it is. [8]

In preclinical experiments, researchers identified 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), derived from pomegranate leaves and branches, as a compound that disrupted pre-formed TTR fibrils in lab tests and reduced TTR deposits while improving survival measures in a worm model. The work also showed disruption of patient-derived cardiac TTR fibrils from a single donor sample, and suggested selectivity compared with amyloid-beta in their assays. This is early research, and the authors noted uncertainties such as bioavailability and the need for more variants and mammalian studies before it can be connected to patient outcomes. [9]

For patients, the case reports mainly serve as reminders that ATTRv can involve multiple body systems and may look different even among people with TTR variants. They may be most relevant to families with rare mutations, but they cannot estimate risk or predict an individual's course. The PGG study is laboratory and animal-model work, so it does not indicate a new treatment option yet; it mostly adds a new idea being explored, aimed at breaking down existing amyloid fibrils, which could matter later only if confirmed in further studies. [7] [8] [9]