Tau in situ hybridization in normal and alzheimer brain: Localization in the somatodendritic compartment

Kosik, Kenneth S.; Crandall, James E.; Mufson, Elliott J.; Neve, Rachael L.

doi:10.1002/ana.410260308

Cited by 81 publications

(40 citation statements)

References 32 publications

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“…Although losses were found to be greatest in regions most affected by neurofibrillary' change, equivalent low levels were also found in brain regions with no extensive PHF accumulation. Athough it is known that tangle-containing cells continue to produce tau protein [38] and dendritic sprouting may occur in Alz heimer's disease [39], the reason for the uniformity is unclear. Decreases in tubulin levels cannot account for the result, since tubulin content is unchanged in Alzhei mer's disease [40], One possibility is that, in Alzheimer's disease, there is a global switch to basal levels of tau syn thesis which appears to be independent of the extent of neurofibrillary pathology, but may be a pre-condition which favours PHF formation in specific brain regions.…”

Section: Discussionmentioning

confidence: 99%

Regional Distribution of Paired Helical Filaments and Normal Tau Proteins in Aging and in Alzheimer's Disease with and without Occipital Lobe Involvement

Mukaetova‐Ladinska

Harrington

Hills

et al. 1992

Dement Geriatr Cogn Disord

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A characteristic hallmark of Alzheimer''s disease is the presence of neurofibrillary tangles which consist of paired helical filaments (PHFs) in the brain. Tau protein, which is normally an axonal microtubule-associated protein, becomes incorporated into PHFs that accumulate in the somatodendritic compartment of neurons in Alzheimer''s disease. We have examined the regional distribution of PHF-bound tau and normal tau proteins in aging and in Alzheimer''s disease using immunoassays which selectively measure these two immunochemically distinct presentations of tau protein in brain tissue. Normal, soluble tau protein levels were decreased in Alzheimer''s disease, the most affected regions being frontal and temporal cortices. Accumulation of tau protein in PHFs, that was restricted largely to the grey matter, was greatest in entorhinal and temporal cortices. The PHF-bound tau content, measured biochemically, matched the neurofibrillary pathology observed immunohistochemically. In 2 out of 14 Alzheimer''s disease cases, very high PHF levels were observed in the occipital lobe. This correlated with an abundance of tau-immunoreactive dystrophic neurites throughout the neuropil and around neuritic plaques in the absence of significant numbers of neurofibrillary tangles.

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Section: Discussionmentioning

confidence: 99%

Regional Distribution of Paired Helical Filaments and Normal Tau Proteins in Aging and in Alzheimer's Disease with and without Occipital Lobe Involvement

Mukaetova‐Ladinska

Harrington

Hills

et al. 1992

Dement Geriatr Cogn Disord

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“…] For immunofluorescence, cultures were fixed with 4% paraformaldehyde in TBS for 5 minutes at room temperature. The cultures were then rinsed twice for 5 minutes in TBS, blocked for 30 minutes in TBS containing 1% bovine serum albumin (BSA) and 2% normal goat serum and incubated overnight at 4°C in TBS containing 1% BSA and 1:100 dilutions of RT97, L3, a polyclonal antibody directed against beta-tubulin (Sigma) and monoclonal antibodies directed against phosphorylated (PHF-1) (Greenburg and Davies, 1990), nonphosphorylated (Tau-1) (Kosik et al, 1989) and phosphoindependent (5E2) (Joachim et al, 1987) epitopes of tau. The following morning, cultures were rinsed three times with TBS, reblocked for 30 minutes, rinsed with TBS, then incubated for 30 minutes at 37°C in TBS containing 1% BSA and a 1:150 dilution of Texas Red conjugated goat anti-rabbit IgG.…”

Section: Immunoblot Analysis and Immunofluorescencementioning

confidence: 99%

Mitogen-activated protein kinase regulates neurofilament axonal transport

Chan

Dickerson

Ortiz

et al. 2004

Journal of Cell Science

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Mitogen-activated protein kinase (MAP) kinase plays a pivotal role in the development of the nervous system by mediating both neurogenesis and neuronal differentiation. Here we examined whether p42/44 MAP kinase plays a role in axonal transport and the organization of neurofilaments (NFs) in axonal neurites. Dominant-negative p42/44 MAP kinase, anti-MAP kinase antisense oligonucleotides and the MAP kinase inhibitor PD98059 all reduced NF phospho-epitopes and inhibited anterograde NF axonal transport of GFP-tagged NF subunits in differentiated NB2a/d1 neuroblastoma cells. Expression of constitutively active MAP kinase and intracellular delivery of active enzyme increased NF phospho-epitopes and increased NF axonal transport. Longer treatment with PD98059 shifted NF transport from anterograde to retrograde. PD98059 did not inhibit overall axonal transport nor compromise overall axonal architecture or composition. The p38 MAP kinase inhibitor SB202190 did not inhibit NF transport whereas the kinase inhibitor olomoucine inhibited both NF and mitochondrial transport. Axonal transport of NFs containing NF-H whose C-terminal region was mutated to mimic extensive phosphorylation was substantially less affected by PD98059 compared to a wild-type construct. These data suggest that p42/44 MAP kinase regulates NF anterograde transport by NF C-terminal phosphorylation. MAP kinase may therefore stabilize developing axons by promoting the accumulation of NFs within growing axonal neurites.

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“…Furthermore, tau mutations cause atypical PD syndromes, such as progressive supranuclear palsy, and corticobasal degeneration (Gozes, 2010). While the hyperphosphorylation of tau causes toxicity (Morris et al, 2011), increasing evidence also supports a possible role for functional loss of tau protein in both diseases, as soluble tau is reduced in the affected regions in both disorders (Lei et al, 2012;Kosik et al, 1989;Zhukareva et al, 2001). We previously reported that tau knockout mouse display progressive motor and cognitive behavioral abnormalities, brain weight loss and brain-wide atrophy, loss of key proteins involved in memory formation, neuronal death in substantia nigra (SN), dopamine loss and tyrosine hydroxylase (TH) terminal loss in the caudate-putamen (CPu), as well as iron accumulation in the brain; all of which are features of neurodegeneration (Lei et al, 2012(Lei et al, , 2014.…”

Section: Introductionmentioning

confidence: 98%

Clioquinol rescues Parkinsonism and dementia phenotypes of the tau knockout mouse

Lei

Ayton

Appukuttan

et al. 2015

Neurobiology of Disease

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Iron accumulation and tau protein deposition are pathological features of Alzheimer's (AD) and Parkinson's diseases (PD). Soluble tau protein is lower in affected regions of these diseases, and we previously reported that tau knockout mice display motor and cognitive behavioral abnormities, brain atrophy, neuronal death in substantia nigra, and iron accumulation in the brain that all emerged between 6 and 12 months of age. This argues for a loss of tau function in AD and PD. We also showed that treatment with the moderate iron chelator, clioquinol (CQ) restored iron levels and prevented neuronal atrophy and attendant behavioral decline in 12-month old tau KO mice when commenced prior to the onset of deterioration (6 months). However, therapies for AD and PD will need to treat the disease once it is already manifest. So, in the current study, we tested whether CQ could also rescue the phenotype of mice with a developed phenotype. We found that 5-month treatment of symptomatic (13 months old) tau KO mice with CQ increased nigral tyrosine hydroxylase phosphorylation (which induces activity) and reversed the motor deficits. Treatment also reversed cognitive deficits and raised BDNF levels in the hippocampus, which was accompanied by attenuated brain atrophy, and reduced iron content in the brain. These data raise the possibility that lowering brain iron levels in symptomatic patients could reverse neuronal atrophy and improve brain function, possibly by elevating neurotrophins.

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Tau in situ hybridization in normal and alzheimer brain: Localization in the somatodendritic compartment

Cited by 81 publications

References 32 publications

Regional Distribution of Paired Helical Filaments and Normal Tau Proteins in Aging and in Alzheimer's Disease with and without Occipital Lobe Involvement

Regional Distribution of Paired Helical Filaments and Normal Tau Proteins in Aging and in Alzheimer's Disease with and without Occipital Lobe Involvement

Mitogen-activated protein kinase regulates neurofilament axonal transport

Clioquinol rescues Parkinsonism and dementia phenotypes of the tau knockout mouse

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