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PubMed This is a summary of 9 peer-reviewed journal articles Updated
Neurology · Multiple System Atrophy - Parkinsonian type

The Biology of MSA-P: Why It Differs from Parkinson's

At a Glance

MSA-P and Parkinson's are both caused by the alpha-synuclein protein, but they behave differently. In Parkinson's, the protein damages neurons directly. In MSA-P, a more aggressive form of the protein destroys oligodendrocytes, which are the essential support cells that insulate nerves.

To understand Multiple System Atrophy - Parkinsonian type (MSA-P), it helps to look under the microscope. While it shares many symptoms with Parkinson’s disease, the biological “engine” driving the two conditions is fundamentally different. Both are classified as synucleinopathies because they involve a protein called alpha-synuclein, but the way this protein behaves—and which cells it attacks—sets them apart [1][2].

The Role of Alpha-Synuclein

In a healthy brain, alpha-synuclein is a normal protein that helps nerves communicate. In diseases like MSA and Parkinson’s, this protein “misfolds,” becoming sticky and clumping together into toxic piles [3].

However, the “strains” of misfolded alpha-synuclein in MSA are much more aggressive than those found in Parkinson’s [4]. Think of the Parkinson’s protein as a slow-moving ember, while the MSA protein is more like a fast-moving wildfire. This higher “toxicity” is why MSA typically progresses more rapidly [3].

Neurons vs. Support Cells

The most critical difference between the two diseases is the location of these protein clumps.

  • In Parkinson’s Disease: The clumps (called Lewy bodies) form inside neurons—the primary cells that send signals throughout the brain [5].
  • In MSA-P: The clumps form primarily in oligodendrocytes [1]. These are not the nerves themselves, but “support cells” (a type of glia) that act like the rubber insulation on an electrical wire [6].

When these clumps—technically called Glial Cytoplasmic Inclusions (GCIs)—build up, the oligodendrocytes can no longer provide the “insulation” (myelin) that nerves need to function [7]. Eventually, without their support system, the nerves themselves begin to wither and die [6].

MSA-P vs. MSA-C: Location Matters

You may hear about two types of MSA: MSA-P (Parkinsonian) and MSA-C (Cerebellar). Biologically, they are the same disease—they both involve the same GCI clumps in the support cells [8].

The difference is simply where the damage is most concentrated:

  • MSA-P: The damage is mostly in the striatonigral system, the area of the brain that controls movement and causes Parkinson-like stiffness and slowness [8].
  • MSA-C: The damage is mostly in the olivopontocerebellar system, which controls balance and coordination, leading to “ataxia” or a drunken-like gait [8][9].

Understanding that MSA-P is a disease of the “insulation” rather than just the “wires” helps explain why it is so complex and why treatments that work for Parkinson’s (which target the “wires”) may not be as effective for MSA [2][5].

Common questions in this guide

How is MSA-P different from Parkinson's disease?
While both conditions involve the alpha-synuclein protein, Parkinson's damages the neurons themselves. MSA-P primarily damages oligodendrocytes, which are support cells that provide essential insulation for your nerves.
What is the difference between MSA-P and MSA-C?
Both are forms of Multiple System Atrophy, but they affect different parts of the brain. MSA-P primarily impacts the striatonigral system, causing Parkinson-like movement issues. MSA-C affects the olivopontocerebellar system, causing problems with balance and coordination.
Why does MSA progress faster than Parkinson's?
The misfolded alpha-synuclein protein in MSA is more aggressive and toxic than the form found in Parkinson's disease. This highly toxic structure causes the disease to spread and cause neurological damage more rapidly.
Why don't Parkinson's medications work as well for MSA-P?
Parkinson's treatments primarily target the nerve cells to replace lost dopamine. Because MSA-P damages the underlying support cells that keep those nerves alive, standard Parkinson's treatments are often less effective.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does my clinical presentation suggest more involvement of the striatonigral system (MSA-P) or the olivopontocerebellar system (MSA-C)?
  2. 2.Is there evidence of 'hot cross bun' sign or putaminal atrophy on my MRI that supports the biological diagnosis of MSA?
  3. 3.Since MSA affects support cells (oligodendrocytes) rather than just neurons, how does that change the way we monitor my progression compared to someone with Parkinson's?
  4. 4.Does the 'prion-like' nature of alpha-synuclein in MSA mean that we should expect a different response to experimental therapies currently targeting alpha-synuclein?

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 (9)
  1. 1

    Chemical disaggregation of alpha-synuclein fibrils as a therapy for synucleinopathies.

    Wu S, Hernandez Villegas NC, Schekman R

    Proceedings of the National Academy of Sciences of the United States of America 2023; (120(11)):e2300965120 doi:10.1073/pnas.2300965120.

    PMID: 36888654
  2. 2

    Signs of early cellular dysfunction in multiple system atrophy.

    Herrera-Vaquero M, Heras-Garvin A, Krismer F, et al.

    Neuropathology and applied neurobiology 2021; (47(2)):268-282 doi:10.1111/nan.12661.

    PMID: 32892415
  3. 3

    Disease Mechanisms of Multiple System Atrophy: What a Parallel Between the Form of Pasta and the Alpha-Synuclein Assemblies Involved in MSA and PD Tells Us.

    Melki R

    Cerebellum (London, England) 2024; (23(1)):13-21 doi:10.1007/s12311-022-01417-0.

    PMID: 35657577
  4. 4

    Brain injections of glial cytoplasmic inclusions induce a multiple system atrophy-like pathology.

    Teil M, Dovero S, Bourdenx M, et al.

    Brain : a journal of neurology 2022; (145(3)):1001-1017 doi:10.1093/brain/awab374.

    PMID: 35285474
  5. 5

    Cerebral Astrocytic Phosphorylated-α-Synuclein Accumulation in Multiple System Atrophy With Long Clinical Course.

    Sakai K

    Neuropathology : official journal of the Japanese Society of Neuropathology 2025; (45(5)):e70026 doi:10.1111/neup.70026.

    PMID: 40998529
  6. 6

    SNCA and TPPP transcripts increase in oligodendroglial cytoplasmic inclusions in multiple system atrophy.

    Kon T, Forrest SL, Lee S, et al.

    Neurobiology of disease 2024; (198()):106551 doi:10.1016/j.nbd.2024.106551.

    PMID: 38839023
  7. 7

    Parkinson's disease and multiple system atrophy patient iPSC-derived oligodendrocytes exhibit alpha-synuclein-induced changes in maturation and immune reactive properties.

    Azevedo C, Teku G, Pomeshchik Y, et al.

    Proceedings of the National Academy of Sciences of the United States of America 2022; (119(12)):e2111405119 doi:10.1073/pnas.2111405119.

    PMID: 35294277
  8. 8

    Multiple system atrophy.

    Goh YY, Saunders E, Pavey S, et al.

    Practical neurology 2023; (23(3)):208-221 doi:10.1136/pn-2020-002797.

    PMID: 36927875
  9. 9

    The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy.

    Wenning GK, Stankovic I, Vignatelli L, et al.

    Movement disorders : official journal of the Movement Disorder Society 2022; (37(6)):1131-1148 doi:10.1002/mds.29005.

    PMID: 35445419

This page explains the biology of MSA-P for educational purposes only. It does not replace professional medical advice from your neurologist or care team.

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