Acta Neuropathologica: SFPQ and Tau: Key factors leading to the rapid development of Alzheimer's disease.

Dysfunctional RNA binding proteins (RBPs) are associated with several neurodegenerative disorders.
recently this research paradigm has been extended to the pathophysiology of Alzheimer's disease (AD).
AD is the most common form of dementia, associated with aggressive neurodegenerative changes that affect more than 40 million people worldwide.
, cases of circulating AD are characterized by slow cognitive decline and the duration of the disease after clinical symptoms occur is approximately 8 years.
, however, there is growing evidence of differences in clinical esolyses and progression rates.
recently, a rapidly developing AD (rpAD) was identified as a micropsychiatric examination (MMSE: a psychometric test) score that dropped sharply (e.g., by 5 minutes/year), and/or the duration of the disease decreased (approximately 4 years).
in different literature studies, the clinical definition of rpAD varies widely.
preliminary evidence provides a compelling view that rpAD is associated with unique molecular and disease-relevant cascades.
, no significant differences were found in the core neuropathological characteristics between spAD and rpAD, suggesting a need to understand the underlying pathogenic mechanisms that lead to this heterogeneity.
paper, the authors identified disease subtype-specific variations of the disease-binding proteomics (RBPome) of exudable AD (spAD), rapidly carrying AD (rpAD) and exudable Creutzfeldt Jakob disease (sCJD), as well as controlled cases using RNA drop-down analysis to bind proteomics.
authors found that one of the proteins identified, the shear factor proline and glutamine-rich (SFPQ), was reduced in post-mortem expression in fast-moving AD patients, sCJD patients, and 3xTg mice in the advanced stages of the disease.
, 3xTg mice showed increased expression of SFPQ in the early stages of the disease and after in-body oxidative stress stimulation.
note that in the brains of rpAD patients, SFPQ showed significant nuclear misalposition and co-location with TIA-1 cytones.
addition, SFPQ and p-tau are shown to be extra-nuclear co-location in rpAD brain injury.
note that the link between SFPQ and tau oligomers in the rpAD brain suggests that SFPQ may play a role in the oligomering of tau proteins and subsequent misfolding.
Is consistent with the results from the human brain, in-body studies in this paper show that SFPQ is recruited into TIA-1 positive stress particles (SGs) after oxidative stress induction, and co-located with tau/p-tau in these particles, providing a possible mechanism for causing SFPQ misalposition through pathological SGs.
addition, in-body expression of human tau induced SFPQ significantly reduced, suggesting that tau in the SFPQ downward play a causal role.
current results suggest that SFPQ imbalances and dislocations, subsequent DNA-related abnormalities, and the abnormal dynamics associated with pathological tau by SGs are important ways to lead to rapid AD progression.
: Patient queue processing, neuropathological examination, and brain tissue collection in this study were carried out in accordance with the previous description.
the time interval between 3 to 18h, spAD and rpAD are AD, Braak phased , AD subsype samples have no common pathological changes.
, the sCJD subsype (sCJD-MM1 and -VV2) is also completely composed of the primary pathogenesis.
cases were confirmed by neuropathological examinations in 25 regions of the cerebral cortical, healing, intercity, cer cerebrocephalus and brain trunk.
studied sumutrine and Irine, Klüver-barera, and immunobiochemic chemistry (for glial fibroic acidic proteins, beta-amyloid proteins, phosphorylation τ, alpha-synthesized nucleoproteins, TDP 43, ubimin, p62, and small glial cell-specific markers).
neuropathological assessment of spAD was carried out after the Braak and Braak phases.
all rpAD cases meet the current standards of rpAD.
no significant difference in age distribution.
, parallel to the results of the human brain study, in-body studies (stress cell models) in this paper clearly show that after oxidative stress therapy, SFPQ and p-tau are converted to CYM TIA-1-positive SGs.
in-body expression human tau (tau pathological model) can induce a significant reduction in SFPQ, suggesting the role of tau in SFPQ downgrade.
, the 3xTg mouse model study specifically revealed very early changes in target proteon characteristics.
in mouse models of 3xTg, the expression of SFPQ and TIA-1 has increased significantly in the early stages of the disease, suggesting that these proteins may have potential potential as targets for early treatment.
Younas, N., Zafar, S., Shafiq, M. et al. SFPQ and Tau: critical factors to rapid progression of Alzheimer's disease. Acta Neuropathol 140, 317-339 (2020). Source: MedSci Originals !-- Content Presentation Ends -- !-- To Determine If Login Ends.