# Analysis of Lumbar Spine Stenosis Specimens for Identification of Transthyretin Cardiac Amyloidosis

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $685,665

## Abstract

Project Summary/Abstract
Transthyretin (TTR) amyloidosis (ATTR) is a form of systemic amyloidosis either caused by mutations in the
TTR gene leading to aggregation and variant TTR amyloidosis (ATTRv; v is for variant) or from aggregation of
wild type TTR leading to ATTRwt amyloidosis. ATTRwt is becoming the most common form of systemic
amyloidosis, principally because of the aging of the population. ATTRwt cardiac amyloidosis (ATTRwt-CA)
almost exclusively affects individuals who >60 years and the average age at diagnosis is 77 years. Orthopedic
manifestations (carpal tunnel syndrome (CTS) often bilaterally, biceps tendon rupture, joint replacements [hip,
knee, and shoulder] and lumbar spinal stenosis (LSS)) are collectively found in >80% of patients with ATTRwt-
CA. Affected individuals experience these orthopedic manifestations on 5 to 15 years prior to the diagnosis of
ATTR-CA. Our preliminary data from a NIA R21 grant (AG058348) shows that amyloid deposits are a common
cause of lumbar spinal stenosis and that a majority but not all amyloid deposits are due to TTR. The presence
of TTR amyloid in the lumbar spine could portend ATTR-CA in the future. Accordingly, we propose to conduct
a multi-center, prospective cohort study aimed at facilitating identification of individuals with ATTR-CA. The
aims of the study are: (1) To identify subjects with previous LSS Surgery who have evidence of TTR amyloid
deposits in their spinal specimens and could be at risk for ATTR-CA, and (2) To evaluate for ATTR-CA among
those with localized TTR in their spinal tissue. The hypotheses to be tested are (1) that at least 30% of spinal
samples will demonstrate amyloid and more than half of those with amyloid will be due to TTR as determined
by mass spectrometry and (2) that more than 20% of patients with TTR amyloid deposits in their spine will
have scintigraphy evidence of ATTR-CA, 5 to 15 years after spinal surgery as compared to <5% with
indeterminant type of amyloid in spinal tissue. We will also evaluate the cost effectiveness of this screening
approach. An exploratory aim is to evaluate an artificial intelligence technique for pathologic that can identify
amyloid histologically without Congo Red staining. By systematically evaluating older adults with LSS who
have previously undergone lumbar spine surgery thorough pathological evaluation for amyloid in surgically
obtained tissue, and if amyloid is present, performing tissue typing with mass spectrometry, there's a unique
opportunity to identify older adults with ATTR-CA early in the course of the illness. Early identification of
affected individuals is key because disease modifying therapies are significantly more effective before
significant cardiac dysfunction has occurred. The data collected in the planned studies could change clinical
practice. By routinely evaluating LS specimens for amyloid and determining the precursor protein, we could
facilitate early identification of those who develop ATTR-CA, a diso...

## Key facts

- **NIH application ID:** 10851722
- **Project number:** 5R01AG081582-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** MATHEW S MAURER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $685,665
- **Award type:** 5
- **Project period:** 2023-06-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851722

## Citation

> US National Institutes of Health, RePORTER application 10851722, Analysis of Lumbar Spine Stenosis Specimens for Identification of Transthyretin Cardiac Amyloidosis (5R01AG081582-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10851722. Licensed CC0.

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