A Western Australian kindred with Dutch cerebral amyloid angiopathy

Panegyres, Peter K.; Schofield, Peter R.; Blumbergs, Peter

doi:10.1016/j.jns.2005.08.002

Cited by 12 publications

(7 citation statements)

References 22 publications

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“…As regards WMC, frequency was 50%, which may be underscored since MRI were performed in only 7/12 patients (Table 1). This result may explain a slightly inferior frequency compared with the 60 to 100% frequency based on MRI studies in patients carrying APP mutations associated with CAA (Roks et al, 2000;Greenberg et al, 2003;Rossi et al, 2004;Panegyres et al, 2005;van den Boom et al, 2005). As in our cases (Fig.…”

Section: Discussioncontrasting

confidence: 57%

Phenotype associated with APP duplication in five families

Cabrejo¹,

Guyant‐Maréchal

Laquerrière³

et al. 2006

Brain

237

181

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Different duplications of the APP locus have been identified in five families with autosomal dominant early onset Alzheimer's disease (ADEOAD) and Abeta-related cerebral amyloid angiopathy (CAA). This study describes the phenotype of this new entity. Clinical, neuropsychological, imagery and neuropathological data were reviewed. The phenotype was not dependent on the size of the duplication and there was no clinical feature of Down's syndrome. Dementia was observed in all cases; intracerebral haemorrhage (ICH) was reported in 6 (26%) and seizures occurred in 12 (57%) of 21 patients. Age of onset of dementia ranged from 42 to 59 years, ICH from 53 to 64 years and age at death from 46 to 75 years. The neuropathological findings in five cases demonstrated Alzheimer's disease and severe CAA lesions that were reminiscent from those reported in brains of Down's syndrome patients. A striking feature consisted in intraneuronal Abetax-40 accumulation located in the granular cell layer of the dentate gyrus and in the pyramidal cell layer of the Ammon's horn.

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Section: Discussioncontrasting

confidence: 57%

Phenotype associated with APP duplication in five families

Cabrejo¹,

Guyant‐Maréchal

Laquerrière³

et al. 2006

Brain

237

181

View full text Add to dashboard Cite

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“…A rough estimate is that likely 400-500 persons are at risk in multigenerational offspring families, but no clear data are available at this moment. An affected family described in Western Australia originates from Katwijk (Panegyres et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Amyloid β in hereditary cerebral hemorrhage with amyloidosis-Dutch type

Kamp

Moursel²,

Haan³

et al. 2014

Reviews in the Neurosciences

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“…Brain imaging examinations (CT and MRI) showed cerebral hemorrhages. The reported neuropathological characteristics included hemorrhages, no NFTs, amyloid plaques, and CAA [102, 108-114]. Studies of APP processing in cellular models showed that the total secreted Aβ and Aβ38 did not change compared to the WT control; secreted Aβ40 and Aβ42 decreased; the ratio of Aβ42/Aβ40 decreased; Aβ40 polymerization increased; and the resistance to proteolytic degradation with neprilysin increased [86, 91, 104].…”

Section: The Function and Processing Of Normal Appmentioning

confidence: 99%

Processing of Mutant β-Amyloid Precursor Protein and the Clinicopathological Features of Familial Alzheimer’s Disease

Bi¹,

Bi²,

Li³

2019

Aging and disease

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Alzheimer’s disease (AD) is a complex, multifactorial disease involving many pathological mechanisms. Nonetheless, single pathogenic mutations in amyloid precursor protein (APP) or presenilin 1 or 2 can cause AD with almost all of the clinical and neuropathological features, and therefore, we believe an important mechanism of pathogenesis in AD could be revealed from examining pathogenic APP missense mutations. A comprehensive review of the literature, including clinical, neuropathological, cellular and animal model data, was conducted through PubMed and the databases of Alzforum mutations, HGMD, UniProt, and AD&FTDMDB. Pearson correlation analysis combining the clinical and neuropathological data and aspects of mutant APP processing in cellular models was performed. We find that an increase in Aβ42 has a significant positive correlation with the appearance of neurofibrillary tangles (NFTs) and tends to cause an earlier age of AD onset, while an increase in Aβ40 significantly increases the age at death. The increase in the α-carboxyl terminal fragment (CTF) has a significantly negative correlation with the age of AD onset, and β-CTF has a similar effect without statistical significance. Animal models show that intracellular Aβ is critical for memory defects. Based on these results and the fact that amyloid plaque burden correlates much less well with cognitive impairment than do NFT counts, we propose a “snowball hypothesis”: 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.

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A Western Australian kindred with Dutch cerebral amyloid angiopathy

Cited by 12 publications

References 22 publications

Phenotype associated with APP duplication in five families

Phenotype associated with APP duplication in five families

Amyloid β in hereditary cerebral hemorrhage with amyloidosis-Dutch type

Processing of Mutant β-Amyloid Precursor Protein and the Clinicopathological Features of Familial Alzheimer’s Disease

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