A comparative study of histological and immunohistochemical methods for neurofibrillary tangles and senile plaques in Alzheimer's disease

Vallet, Philippe; Guntern, R.; Hof, Patrick R.; Golaz, Jean; Delacourte, André; Robakis, Nikolaos K.; Bouras, Constantin

doi:10.1007/bf00308476

Cited by 156 publications

(89 citation statements)

References 37 publications

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“…There were no statistically significant differences in the numbers of neurofibrillary tangles in several cortical regions among APOE3/3, -3/4, and 4/4 genotypes. The literature suggests that neurofibrillary tangles are endpoints of neuronal injury in a variety of neurodegenerative illnesses (37)(38)(39). The counts in the various cortical regions examined correlated strongly with duration of illness (P < 0.01) in the patients in this study.…”

supporting

confidence: 58%

Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.

Schmechel

Saunders

Strittmatter

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

1,354

707

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Amyloid -peptide (AP) deposition in senile plaques and cerebral vessels is a neuropathological feature of Alzheimer disease (AD). We examined the possibility that commonly observed variability in Af8 deposition in late-onset AD might be related to apolipoprotein E genotype (APOE gene; the two most common alleles are 3 and 4), since APOE4 is a susceptibility gene for late-onset AD and apolipoprotein E interacts strongly with A.8 in vitro. In an autopsy series of brains of late-onset AD patients, we found a strong association of APOE4 allele with increased vascular and plaque Af3 deposits. Late-onset AD patients with one or two APOE4 alleles have a distinct neuropathological phenotype compared with patients homozygous for APOE3.

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supporting

confidence: 58%

Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.

Schmechel

Saunders

Strittmatter

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

1,354

707

View full text Add to dashboard Cite

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“…Cells were immunostained with an antibody that recognizes total tau and counterstained with thioflavin-S. Thioflavin-S binding is a known indicator of insoluble protein aggregates with ␤-pleated sheet structure (38), and thioflavin-S readily stains the intracellular neurofibrillary tangles in Alzheimer's disease brain (39). Thioflavin-S-positive inclusions were not observed in cells transfected with either the fulllength or Asp-421-truncated tau constructs alone (Fig.…”

Section: Co-transfection With Gsk3␤ Results In the Formation Of Thiofmentioning

confidence: 99%

Glycogen Synthase Kinase 3β Induces Caspase-cleaved Tau Aggregation in Situ

Cho¹,

Johnson

2004

Journal of Biological Chemistry

110

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Tau is a substrate of caspases, and caspase-cleaved tau has been detected in Alzheimer's disease brain but not in control brain. Furthermore, in vitro studies have revealed that caspase-cleaved tau is more fibrillogenic than full-length tau. Considering these previous findings, the purpose of this study was to determine how the caspase cleavage of tau affected tau function and aggregation in a cell model system. The effects of glycogen synthase kinase 3␤ (GSK3␤), a well established tau kinase, on these processes also were examined. Tau or tau that had been truncated at Asp-421 to mimic caspase cleavage (Tau-D421) was transfected into cells with or without GSK3␤, and phosphorylation, microtubule binding, and tau aggregation were examined. Tau-D421 was not as efficiently phosphorylated by GSK3␤ as fulllength tau. Tau-D421 efficiently bound microtubules, and in contrast to the full-length tau, co-expression with GSK3␤ did not result in a reduction in the ability of Tau-D421 to bind microtubules. In the absence of GSK3␤, neither Tau-D421 nor full-length tau formed Sarkosyl-insoluble inclusions. However, in the presence of GSK3␤, Tau-D421, but not full-length tau, was present in the Sarkosyl-insoluble fraction and formed thioflavin-Spositive inclusions in the cell. Nonetheless, co-expression of GSK3␤ and Tau-D421 did not result in an enhancement of cell death. These data suggest that a combination of phosphorylation events and caspase activation contribute to the tau oligomerization process in Alzheimer's disease, with GSK3␤-mediated tau phosphorylation preceding caspase cleavage.

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“…Silver staining of tissues was achieved using an adapted version of the Campbell-Switzer silver stain protocol (67). Briefly, tissue sections were treated with 2% ammonium hydroxide, rinsed in water, then placed in silver-pyridine-carbonate solution (0.5% silver nitrate, 0.4% potassium carbonate, 0.14% pyridine) for 40 min in the dark.…”

Section: Methodsmentioning

confidence: 99%

Robust Central Nervous System Pathology in Transgenic Mice following Peripheral Injection of α-Synuclein Fibrils

Ayers

Brooks

Rutherford

et al. 2017

J Virol

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Misfolded ␣-synuclein (␣S) is hypothesized to spread throughout the central nervous system (CNS) by neuronal connectivity leading to widespread pathology. Increasing evidence indicates that it also has the potential to invade the CNS via peripheral nerves in a prion-like manner. On the basis of the effectiveness following peripheral routes of prion administration, we extend our previous studies of CNS neuroinvasion in M83 ␣S transgenic mice following hind limb muscle (intramuscular [i.m.]) injection of ␣S fibrils by comparing various peripheral sites of inoculations with different ␣S protein preparations. Following intravenous injection in the tail veins of homozygous M83 transgenic (M83 ϩ/ϩ ) mice, robust ␣S pathology was observed in the CNS without the development of motor impairments within the time frame examined. Intraperitoneal (i.p.) injections of ␣S fibrils in hemizygous M83 transgenic (M83 ϩ/Ϫ ) mice resulted in CNS ␣S pathology associated with paralysis. Interestingly, injection with soluble, nonaggregated ␣S resulted in paralysis and pathology in only a subset of mice, whereas soluble Δ71-82 ␣S, human ␤S, and keyhole limpet hemocyanin (KLH) control proteins induced no symptoms or pathology. Intraperitoneal injection of ␣S fibrils also induced CNS ␣S pathology in another ␣S transgenic mouse line (M20), albeit less robustly in these mice. In comparison, i.m. injection of ␣S fibrils was more efficient in inducing CNS ␣S pathology in M83 mice than i.p. or tail vein injections. Furthermore, i.m. injection of soluble, nonaggregated ␣S in M83 ϩ/Ϫ mice also induced paralysis and CNS ␣S pathology, although less efficiently. These results further demonstrate the prion-like characteristics of ␣S and reveal its efficiency to invade the CNS via multiple routes of peripheral administration. IMPORTANCEThe misfolding and accumulation of ␣-synuclein (␣S) inclusions are found in a number of neurodegenerative disorders and is a hallmark feature of Parkinson's disease (PD) and PD-related diseases. Similar characteristics have been observed between the infectious prion protein and ␣S, including its ability to spread from the peripheral nervous system and along neuroanatomical tracts within the central nervous system. In this study, we extend our previous results and investigate the efficiency of intravenous (i.v.), intraperitoneal (i.p.), and intramuscular (i.m.) routes of injection of ␣S fibrils and other protein controls. Our data reveal that injection of ␣S fibrils via these peripheral routes in ␣S-overexpressing mice are capable of inducing a robust ␣S pathology and in some cases cause paralysis. Furthermore, soluble, nonaggregated ␣S also induced ␣S pathology, albeit with much less efficiency. These findings further support and extend the idea of ␣S neuroinvasion from peripheral exposures.

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A comparative study of histological and immunohistochemical methods for neurofibrillary tangles and senile plaques in Alzheimer's disease

Cited by 156 publications

References 37 publications

Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.

Increased amyloid beta-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease.

Glycogen Synthase Kinase 3β Induces Caspase-cleaved Tau Aggregation in Situ

Robust Central Nervous System Pathology in Transgenic Mice following Peripheral Injection of α-Synuclein Fibrils

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