Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology

  title={Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology},
  author={Peter L. Lantos and Philip J. Luthert and Diane P. Hanger and B. H. Anderton and Michael John Mullan and Martin N. Rossor},
  journal={Neuroscience Letters},
Processing of Mutant β-Amyloid Precursor Protein and the Clinicopathological Features of Familial Alzheimer’s Disease
A “snowball hypothesis” is proposed: the accumulation of intraneuronal NFTs caused by extracellular Aβ42 and the increase in intraneURonal APP proteolytic products (CTFs and Aβs) could cause cellular organelle stress that leads to neurodegeneration in AD, which then resembles the formation of abnormal protein ”snowballs” both inside and outside of neurons.
Variations in the neuropathology of familial Alzheimer’s disease
Additional frontotemporal neuronal loss in association with increased tau pathology appears unique to PSEN mutations, with mutations in exons 8 and 9 having enlarged cotton wool plaques throughout their cortex.
Prominent amyloid plaque pathology and cerebral amyloid angiopathy in APP V717I (London) carrier – phenotypic variability in autosomal dominant Alzheimer’s disease
The detailed clinical and neuropathologic characterization of an APP V717I carrier is presented, which reveals important novel insights into the phenotypic variability of ADAD cases and demonstrates striking phenotypesic variability inADAD cases.
Lewy body and Alzheimer pathology in a family with the amyloid-β precursor protein APP717 gene mutation
Observations suggest an association between the chromosome 21 APP mutation and Lewy body formation, possibly mediated by other environmental or genetic factors.
The Amyloid Peptide and Its Precursor in Alzheimer's Disease
  • J. Octave
  • Biology
    Reviews in the neurosciences
  • 1995
expression in transgenic mice of both mutated amyloid peptide precursor and amyloids associated proteins should prove useful for examining the importance of putative etiological factors, and for testing novel therapies including anti-amyloidogenic strategies.


A4 Protein in Alzheimer's Disease: Primary and Secondary Cellular Events in Extracellular Amyloid Deposition
The presence of α1-antichymotrypsin, complement factors and P component, but not of common serum proteins in both the amorphous and congophilic plaques, indicates that these three proteins may have a pathogenetic role in amyloid formation.
A68 proteins in Alzheimer's disease are composed of several tau isoforms in a phosphorylated state which affects their electrophoretic mobilities.
The results further support the notion that PHF contain abnormally phosphorylated tau in an aggregated state, and indicate that these abnormally phosphate-filled tau forms are composed of several tau isoforms and that the full length of the tau molecule is present in these polypeptides.
Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease.
A peptide derived from the amyloid precursor may be neurotoxic, and conditioned medium from these cells was toxic to neurons in primary hippocampal cultures, and the toxic agent could be removed by immunoabsorption with an antibody directed against theAmyloid polypeptide.
Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
It is demonstrated that in this kindred, which shows linkage to chromosome 21 markers, there is a point mutation in the APP gene that causes an amino-acid substitution close to the carboxy terminus of the β-amyloid peptide.
Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease.
Immunocytochemical studies of brain tissue from 26 patients with Down's syndrome showed that the deposition of A4 protein amyloid began in these patients approximately 50 years earlier than it began in 127 normal aging subjects studied previously, although the rate of deposition was the same.
A4 amyloid protein deposition and the diagnosis of Alzheimer's disease
If A4 protein deposition is accepted as a definitive marker for AD, then the age-related prevalence of AD increases dramatically, and to what degree these prevalence rates are reflected in clinically detectable impairment of higher cortical function remains to be determined.
Tau in Alzheimer's disease and Down's syndrome is insoluble and abnormally phosphorylated.
It is concluded that, in Alzheimer's disease, a fraction of tau has a modified phosphorylation state and a decreased solubility; these modifications may precede formation of the neurofibrillary tangles characteristic of Alzheimer’s disease and Down's syndrome in adults.
Effects of injected Alzheimer beta-amyloid cores in rat brain.
Results indicate a neuronal response to amyloid, when preparations of mature plaque amyloids isolated from the AD brain are injected into the rat brain, and exert neurotoxic effects and induce antigens found in theAD brain.
Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder
The inheritance of five polymorphic DNA markers from the proximal long arm of chromosome 21 in a large unselected series of pedi-grees with familial Alzheimer's disease suggests that Alzheimer's Disease is not a single entity, but rather results from genetic defects on chromosome 21 and from other genetic or nongenetic factors.
Alzheimer's paired helical filaments share epitopes with neurofilament side arms.
It is proposed that in tangle‐bearing neurons, neurofilaments are degraded by proteases and that it is fragments of the side arms which contribute to the composition of PHF.