Alzheimer’s Disease

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The most prominent morphological hallmarks of an AD brain are neurofibrillary tangles and neuritic or diffuse plaques. Tangles accumulate inside neurons and consist of hyperphosphorylated tau protein whereas extracellularly located plaques are mainly composed of amyloid-beta (Abeta). Abeta is considered to trigger hyperphosphorylation of tau and dementia in Alzheimer’s disease. With advancing pathology neurons are destroyed by the aggregating proteins. Since dead neurons are hardly regenerated, it is very important to diagnose AD as early as possible. Therefore, we started a project to identify blood biomarkers and to establish diagnostic assays that would allow assessing one’s individual risk to develop AD.
Even if an early diagnosis is possible, it is still necessary to find a treatment strategy that stops disease progression or even prevents its onset. We already showed that the action of specific proteins (ABC transporters) at the blood-brain barrier has a tremendous influence on the accumulation of Abeta in the brain. We also identified plant extracts and a synthetic drug that increase the activity of these transporters. We currently apply for funding for clinical testing of these new options for the patients.

* Project Links:

Read more …  JPND NeuroGem
Read more …  DFG ABC-LRP1 project
Read more …  NFR FRIMEDBIO 2016 project

* Published Research Papers (selection):

  • Short-term effects of microglia-specific mitochondrial dysfunction on amyloidosis in transgenic models of Alzheimer’s disease
    Journal of Alzheimer’s Disease (2018)

    Steffen J, Stenzel J, Ibrahim S, Pahnke J
    65(2):465-474 PubMed PDF

  • Structural studies of amyloid-β peptides: unlocking the mechanism of aggregation and the associated toxicity
    Biochimie (2017)

    Aleksis R, Oleskovs F, Jaudzems K, Pahnke J, Biverstål H
    140:176-192 PubMed PDF

  • Expression of endogenous mouse APP modulates amyloid deposition in hAPP-transgenic mice
    Acta Neuropathologica Com (2017)

    Steffen J, Krohn M, Schwitlick C, Brüning T, Paarmann K, Pietrzik CU, Biverstål H, Jansone B, Langer O, Pahnke J
    5:49 PubMed PDF

  • Revisiting rodent models: Octodon degus as Alzheimer’s disease model?
    Acta Neuropathologica Com (2016)

    Steffen J, Krohn M, Paarmann K, Schwitlick C, Brüning T, Marreiros R, Müller-Schiffmann A, Korth C, Braun K, Pahnke J
    4(1):91 PubMed PDF

  • Accumulation of murine β-amyloid mimics early Alzheimer’s disease.
    Brain (2015)

    Krohn M, Bracke A, Avchalumov Y, Schumacher T, Hofrichter J, Paarmann K, Fröhlich C, Lange C, Brüning T, von Bohlen und Halbach O, Pahnke J
    Aug 138(Pt 8):2370-82. PubMed

  • Alzheimer’s and ABC transporters – new opportunities for diagnostics and treatment.
    Neurobiol Dis (2014)

    Pahnke J, Langer O, Krohn M
    Dec 72 (2014) 54–60. PubMed

  • Alzheimer’s disease and blood-brain barrier function – Why have anti-beta-amyloid therapies failed to prevent dementia progression?
    Neurosci Biobehav Rev (2009)

    Pahnke J, Walker L, Scheffler K, Krohn M
    Jul 33(7): 1099-1108. PubMed PDF

  • Die Funktion der Blut-Hirn-Schranke für die Pathogenese der Alzheimer Demenz – Implikationen für immunologische Therapien zur Plaqueauflösung.
    Fortschr Neurol Psyc (2009)

    Pahnke J, Krohn M, Scheffler K
    Aug 77: S21-24. PubMed