For example, neocortex, hippocampus, brainstem, and cerebellum express comparable levels of Tg tau, but spinal cord expresses ∼60% of those seen in these regions. Figure 1D demonstrates that the expression levels of Tg tau varied in different CNS regions, as revealed by Western blot studies conducted on Tg line 7 with antibodies T6. Using a polyclonal antibody (17026) that recognizes human and mouse tau in quantitative Western blot studies, we showed that the heterozygous Tg mouse lines 7, 43, and 27 overexpressed tau proteins at levels that were approximately 5-, 10-, and 15-fold higher, respectively, than endogenous mouse tau. These data show that tau proteins from all three Tg mouse lines, but not from the wt mouse, are detected by T14, a human tau-specific monoclonal antibody (mAb), and that the dephosphorylated tau bands from the Tg mice align with recombinant fetal human tau. Figure 1C illustrates representative Western blots produced by loading equal amounts of total protein from Tg mice and 9-fold more protein from a wild-type (wt) littermate control, before and after dephosphorylation, into adjacent lanes of a gel followed by electrophoresis and protein transfer to blot membranes. Three stable Tg lines were established that variably overexpressed human tau, as demonstrated by quantitative Western blot analysis of whole-brain extracts from heterozygous Tg mice. These Tg mice recapitulate key features of tauopathies and provide models for elucidating mechanisms underlying diverse tauopathies, including Alzheimer's disease (AD).

Inclusions were present in cortical and brainstem neurons but were most abundant in spinal cord neurons, where they were associated with axon degeneration, diminished microtubules (MTs), and reduced axonal transport in ventral roots, as well as spinal cord gliosis and motor weakness. These mice acquired age-dependent CNS pathology similar to FTDP-17 and ALS/PDC, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Since FTDP-17 tau gene mutations alter levels/functions of tau, we overexpressed the smallest human tau isoform in the CNS of transgenic (Tg) mice to model tauopathies. Filamentous tau aggregates are hallmarks of tauopathies, e.g., frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and amyotrophic lateral sclerosis/parkinsonism–dementia complex (ALS/PDC).

Michael jackson age progression