The scientists examined 1058 proteins in the cerebrospinal fluid of 419 people suffering from Alzheimer's disease. The Alzheimer's subtypes identified showed changes in protein concentrations that were associated with different molecular processes. This mean, that in addition to the characteristic clumping of amyloid and tau proteins in the brain, other inflammatory processes, the growth of inflammatory processes as well as the growth of nerve cells also play a role.  

The identified subtype 1 was characterized by proteins that are associated with neuronal hyperplasticity. Neuronal plasticity describes a dynamic remodeling of already existing synapses. It cannot be equated with the regenerative capacity of neuronal tissue(1). Subtype 2 showed an activation of the innate immune system. Subtype 3 was characterized by RNA dysregulation. RNA dysregulation caused by defective splicing, for example, is also observed in Huntington's disease, a neurodegenerative disorder. During splicing, the non-coding sections of a gene (introns) are cut out of the pre-mRNA and the coding sections (exons) are joined together (2). Subtype 4 showed a dysfunction of the choroid plexus. The choroid plexus is located in the entire system of cerebrospinal fluid-filled cavities of the brain (cerebral ventricles) where it is responsible for the secretion of cerebrospinal fluid (4). Subtype 5 was characterized by an impairment of the blood-brain barrier. It is the border between the blood and the central nervous system through which only certain substances can pass into the brain (5).

Without considering Alzheimer's subtypes, treatment methods could be partially ineffective or only partially effective.

The study has been published in the journal "Nature Aging": Tijms, B.M., Vromen, E.M., Mjaavatten, O. et al. Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles.Nat Aging (2024). https://doi.org/10.1038/s43587-023-00550-7

Further information:
https://www.eurekalert.org/news-releases/1030574

(1) https://flexikon.doccheck.com/de/Neuronale_Plastizit%C3%A4t
(2) https://www.dhh-ev.de/verein/huntington-stiftung
(3) https://www.lecturio.de/artikel/medizin/ventrikelsystem/
(4) https://flexikon.doccheck.com/de/Hirnventrikel#:~:text=The%20ventricular%20system%20consists%20of%204,between%20arachnoid%20and%20pia%20mater.
(5) https://www.gesundheit.gv.at/lexikon/B/lexikon-blut-hirn-schranke.html