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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Hematology

AL, ATTR, and AA: Understanding Your Specific Type

At a Glance

Amyloidosis is a group of diseases caused by misfolded proteins, not a single condition. The most common subtypes are AL, ATTR, and AA. Identifying your exact protein type through specialized testing is mandatory because treatments for one type will not work for another and can be harmful.

“Amyloidosis” is not a single disease; it is an umbrella term for several different conditions. Each type is named after the specific protein that has misfolded [1][2]. Knowing your exact subtype is the most important piece of your diagnosis, as the treatment for one type will not work—and could be dangerous—if used for another [3][4].

The Subtype Matrix

The following table breaks down the “alphabet soup” of the most common types of amyloidosis.

Type The “Bad Actor” Protein Primary Source Major Organs Affected
AL Immunoglobulin Light Chains [5] Plasma cells in bone marrow Heart, Kidneys, Liver, Nerves [6]
ATTRwt Transthyretin (Normal/Wild-type) [7] Liver Heart (usually in older men) [8]
ATTRv Transthyretin (Variant/Genetic) [7] Liver (DNA mutation). Genetic testing and counseling for family is highly recommended. Heart, Nerves, Digestion [9]
AA Serum Amyloid A (SAA) [10] Liver (triggered by inflammation) Kidneys, Digestion, Spleen [11]
ALECT2 Leukocyte Chemotactic Factor 2 [12] Liver Kidneys [13]

Why Subtyping is Mandatory

Doctors must perform amyloid typing to identify the protein before starting any therapy. If a patient with AL amyloidosis is misdiagnosed with ATTR, they might miss out on life-saving chemotherapy [3]. Conversely, giving chemotherapy to a patient who actually has ATTR is unnecessary and potentially toxic [4].

To confirm the type, doctors use specialized tools:

  • Mass Spectrometry: The “gold standard” test that identifies the exact protein in a tissue sample [12].
  • Bone Scintigraphy: A non-invasive scan that can identify ATTR in the heart, but only after AL has been ruled out with blood and urine tests [4][14].

Understanding the Mechanisms

  • AL (Light Chain): This is a plasma cell disorder. Your bone marrow produces “light chain” proteins that don’t fold correctly. Because this involves bone marrow cells, it is managed by hematologists/oncologists [5][6].
  • ATTR (Transthyretin): Transthyretin is a protein that carries Vitamin A and thyroid hormone. In ATTRwt (wild-type), the protein becomes unstable as we age [7]. In ATTRv (variant), a genetic mutation makes the protein unstable from birth, though symptoms may not appear for decades [9].
  • AA (Secondary): This type is a reaction to chronic inflammation. If you have a long-term condition like Rheumatoid Arthritis or a chronic infection, your body produces high levels of SAA protein, which can eventually clump into amyloid deposits [15][16].
  • ALECT2: This is a newer, less common subtype that primarily affects the kidneys. It is most often found in people of Hispanic, Middle Eastern, or North African descent [17][18]. Unlike other types, it is usually slowly progressive and does not involve the heart [13].

Common questions in this guide

Why is it so important to know my exact type of amyloidosis?
Knowing your specific subtype is critical because treatments vary drastically based on the protein involved. A treatment that works for one type, such as chemotherapy for AL amyloidosis, will not work for ATTR and could be dangerous.
What is the difference between AL and ATTR amyloidosis?
AL amyloidosis is caused by misfolded light chain proteins produced in the bone marrow, while ATTR is caused by unstable transthyretin proteins from the liver. Because they originate in different parts of the body, they require completely different medical approaches.
How do doctors determine which type of amyloidosis I have?
Doctors use a process called amyloid typing to identify the exact misfolded protein. The gold standard method is mass spectrometry performed on a tissue sample, though other tools like blood tests, urine tests, and specialized bone scans may also be used.
Is ATTR amyloidosis hereditary?
ATTR amyloidosis can be hereditary. While the wild-type form (ATTRwt) occurs naturally with aging, the variant form (ATTRv) is caused by a genetic mutation present from birth. If you are diagnosed with ATTRv, genetic testing and counseling for your family members is highly recommended.
What causes AA amyloidosis?
AA amyloidosis is triggered by a long-term inflammatory response in the body. If you have a chronic condition like Rheumatoid Arthritis or a chronic infection, your body produces high levels of SAA protein, which can eventually clump into amyloid deposits in your organs.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Which specific protein is causing my amyloidosis, and how was that protein 'typed' (e.g., mass spectrometry or immunohistochemistry)?
  2. 2.Could the treatment for my subtype be harmful if I actually had a different type?
  3. 3.For ATTR: Do I have the 'wild-type' or the 'variant' (hereditary) form, and should my children be tested?
  4. 4.For AA: What is the underlying inflammatory 'trigger' we need to control to stop the amyloid production?
  5. 5.For AL: What is my current light chain level, and how often will we monitor it to see if the treatment is working?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (18)
  1. 1

    Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem cell transplantation: 20-year experience.

    Sanchorawala V, Sun F, Quillen K, et al.

    Blood 2015; (126(20)):2345-7 doi:10.1182/blood-2015-08-662726.

    PMID: 26443620
  2. 2

    18F-Sodium Fluoride PET/MR for the Assessment of Cardiac Amyloidosis.

    Trivieri MG, Dweck MR, Abgral R, et al.

    Journal of the American College of Cardiology 2016; (68(24)):2712-2714 doi:10.1016/j.jacc.2016.09.953.

    PMID: 27978955
  3. 3

    Analysis of the TTR gene in the investigation of amyloidosis: A 25-year single UK center experience.

    Rowczenio D, Quarta CC, Fontana M, et al.

    Human mutation 2019; (40(1)):90-96 doi:10.1002/humu.23669.

    PMID: 30328212
  4. 4

    Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis.

    Gillmore JD, Maurer MS, Falk RH, et al.

    Circulation 2016; (133(24)):2404-12 doi:10.1161/CIRCULATIONAHA.116.021612.

    PMID: 27143678
  5. 5

    The clinical features and outcomes of systemic light chain amyloidosis with hepatic involvement.

    Zhao L, Ren G, Guo J, et al.

    Annals of medicine 2022; (54(1)):1226-1232 doi:10.1080/07853890.2022.2069281.

    PMID: 35481407
  6. 6

    Amyloidosis: a case series and review of the literature.

    Senecal JB, Abou-Akl R, Allevato P, et al.

    Journal of medical case reports 2023; (17(1)):184 doi:10.1186/s13256-023-03886-1.

    PMID: 37081462
  7. 7

    Native State Stabilization of Amyloidogenic Proteins by Kinetic Stabilizers: Inhibition of Protein Aggregation and Clinical Relevance.

    Priyanka , Raymandal B, Mondal S

    ChemMedChem 2024; (19(19)):e202400244 doi:10.1002/cmdc.202400244.

    PMID: 38863235
  8. 8

    Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease.

    Adams D, Koike H, Slama M, Coelho T

    Nature reviews. Neurology 2019; (15(7)):387-404 doi:10.1038/s41582-019-0210-4.

    PMID: 31209302
  9. 9

    Early changes of nerve integrity in preclinical carriers of hereditary transthyretin Ala117Ser amyloidosis with polyneuropathy.

    Chiang MC, Yeh TY, Sung JY, et al.

    European journal of neurology 2021; (28(3)):982-991 doi:10.1111/ene.14698.

    PMID: 33369810
  10. 10

    Amyloid A Amyloidosis.

    Gaffney PM

    Veterinary pathology 2017; (54(1)):5-8 doi:10.1177/0300985816677150.

    PMID: 27879441
  11. 11

    Amyloidosis for the Gastroenterologist: A Comprehensive Systematic Review of Diagnosis and Management of Gastrointestinal Manifestations.

    Tang MJ, Tay TY, Gibbs S, Niewiadomski O

    Journal of gastroenterology and hepatology 2025; (40(12)):2842-2856 doi:10.1111/jgh.70083.

    PMID: 41058263
  12. 12

    Concurrence of leukocyte chemotactic factor 2-associated amyloidosis and autoimmune diseases: A case report.

    Wang S, Yu XJ, Li DY, et al.

    Frontiers in immunology 2022; (13()):966591 doi:10.3389/fimmu.2022.966591.

    PMID: 36059556
  13. 13

    LECT-2 amyloidosis: what do we know?

    Mann BK, Bhandohal JS, Cobos E, et al.

    Journal of investigative medicine : the official publication of the American Federation for Clinical Research 2022; (70(2)):348-353 doi:10.1136/jim-2021-002149.

    PMID: 34848562
  14. 14

    Multidisciplinary Approaches for Transthyretin Amyloidosis.

    Koike H, Okumura T, Murohara T, Katsuno M

    Cardiology and therapy 2021; (10(2)):289-311 doi:10.1007/s40119-021-00222-w.

    PMID: 34089151
  15. 15

    The Clinical Features and Outcomes of Renal Amyloidosis in Tunisia.

    Ayed A, Salem MB, Letaief A, et al.

    Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia 2022; (33(3)):432-439 doi:10.4103/1319-2442.385967.

    PMID: 37843145
  16. 16

    Secondary Amyloidosis Treated with Tocilizumab as a Complication of Temporal Arteritis.

    Kudsi M, Haidar G, Abouharb D, Abouharb L

    European journal of case reports in internal medicine 2024; (11(11)):004895 doi:10.12890/2024_004895.

    PMID: 39525437
  17. 17

    De novo leukocyte chemotactic factor 2 amyloidosis in a pediatric renal allograft, 15 years post-transplant.

    Shamir ER, Lee MM, Walavalkar V

    Pediatric transplantation 2019; (23(3)):e13371 doi:10.1111/petr.13371.

    PMID: 30714275
  18. 18

    Renal leukocyte chemotactic factor 2 (ALECT2)-associated amyloidosis in Chinese patients.

    Li DY, Liu D, Wang SX, et al.

    Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 2020; (27(2)):134-141 doi:10.1080/13506129.2020.1722097.

    PMID: 32024381

This page provides educational information about amyloidosis subtypes and diagnostic typing. It does not replace professional medical advice. Always consult your hematologist or specialist regarding your specific diagnosis, protein typing, and treatment plan.

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