Familial cerebral amyloid angiopathy presenting as recurrent cerebral haemorrhage

Wattendorff, A.R.; Bots, G. Th. A. M.; Went, L. N.; Endtz, L.J.

doi:10.1016/0022-510x(82)90094-6

Cited by 147 publications

(50 citation statements)

References 14 publications

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“…2 and 3; unpublished studies). Recently a similar autosomal dominant cerebral amyloid angiopathy has been described in The Netherlands (4). The histopathology of HCHWA brains is similar to that of the congophilic angiopathy associated with some cases of Alzheimer disease and cases of cerebral hemorrhage caused by sporadic congophilic angiopathy.…”

mentioning

confidence: 62%

Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C).

Ghiso¹,

Jensson²,

Frangione³

1986

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

282

142

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A -trace variant protein is the major constituent of the amyloid fibrils in patients from Iceland with hereditary cerebral hemorrhage with amyloidosis. The protein consists of 110 residues and is similar to human urinary V-trace basic protein (or cystatin C) beginning at its 11th aminoterminal residue. It has an amino acid substitution (glutamine for leucine) at position 58 (position 68 in v-trace numbering), which is near the proposed active site of related proteinsnamely, cysteine protease inhibitors and kininogens. It is postulated that a point mutation has occurred, leading to the production of an unusual protein that is abnormally degraded, bound, and/or precipitated. Alternatively, Vtrace basic protein may be genetically polymorphic, and the variant described here may represent an as-yet-undiscovered isotype or an allelic form that is linked to, but not responsible for, the deposition disease. Our data on the structure of a V-trace variant protein suggests that its gene expresses a polyprotein precursor in which active peptides are flanked by basic amino acid residues that permit cleavage to liberate small internal peptides. It is likely that the nucleotide sequence coding for Arg-Xaa and Lys-Xaa repeated several times in the molecule may function as alternative splicing sites for mRNA processing.Amyloidosis comprises a heterogeneous group of disorders of different etiology characterized by the relentless deposition (mainly extracellular) of a number of fibrillar proteins, which may be distinguished from each other immunohistologically and biochemically. Amyloid fibrils are composed of low molecular weight subunits that originate by polymerization and/or proteolysis of serum proteins. These subunit proteins have a predominant 3-pleated-sheet configuration, as shown by spectroscopic studies and x-ray diffraction (1).Hereditary cerebral hemorrhage with amyloidosis (HCH-WA) is an autosomal dominant form of amyloidosis that is restricted to the cerebral vasculature and leads to hemorrhagic and thrombotic strokes causing death before the age of 40 yr; 128 affected family members within eight families originating from one geographical area in Iceland have been identified (refs. 2 and 3; unpublished studies). Recently a similar autosomal dominant cerebral amyloid angiopathy has been described in The Netherlands (4). The histopathology of HCHWA brains is similar to that of the congophilic angiopathy associated with some cases of Alzheimer disease and cases of cerebral hemorrhage caused by sporadic congophilic angiopathy. In HCHWA there are no plaques or neurofibrillary tangles, and the amount of vascular amyloid is quantitatively much greater than in the two other forms of cerebral amyloid angiopathy (5, 6), making chemical extraction of the amyloid fibrils feasible. We have reported (7) the amino-terminal sequence of the amyloid fibrils obtained from the brain of patients dying of HCHWA. This paper presents the complete primary sequence and discusses its relationship to related proteins and its potential ...

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mentioning

confidence: 62%

Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C).

Ghiso¹,

Jensson²,

Frangione³

1986

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

282

142

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“…FHM was also associated with deafness, retinal degeneration, ataxia, and nystagmus reminiscent of Usher's syndrome in a single complicated family. In addition, CADASIL (cerebral autosomal dominant arteriopathy and stroke with ischemic leukoencephalopathy) caused by Notch-3 gene mutations on chromosome 19p [24] and the Dutch form of hereditary cerebral amyloid angiopathy caused by a point mutation in the amyloid precursor protein gene on chromosome 21 [25] have been associated with migraine.…”

Section: Comorbidity: Migraine Associated With Other Disordersmentioning

confidence: 99%

Migraine comorbidity: from genotype to phenotype

et al. 2000

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“…HCHWA-D patients suffer from hemorrhagic strokes, infarcts, and vascular dementia (Wattendorff et al, 1995). Life expectancy is reduced: the first stroke occurs between the ages of 40 and 65 and is fatal in two thirds of the patients (Wattendorff et al, 1982;. The patients that survive the first hemorrhage suffer from recurrent strokes (Wattendorff et al, 1982).…”

Section: Introductionmentioning

confidence: 99%

“…HCHWA-D is a rare disease and has only been found in three founder families in the Dutch coastal villages of Katwijk and Scheveningen (Wattendorff et al, 1982;. 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.…”

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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Hereditary cerebral hemorrhage with amyloidosis – Dutch type is an autosomal dominant hereditary disease caused by a point mutation in the amyloid precursor protein gene on chromosome 21. The mutation causes an amino acid substitution at codon 693 (E22Q), the ‘Dutch mutation’. Amyloid β, the product after cleavage of the amyloid precursor protein, is secreted into the extracellular space. The Dutch mutation leads to altered amyloid β cleavage and secretion, enhanced aggregation properties, higher proteolysis resistance, lowered brain efflux transporter affinity, and enhanced cell surfaces binding. All these result in amyloid β accumulation in cerebral vessel walls, causing cell death and vessel wall integrity loss, making cerebral vessel walls in hereditary cerebral hemorrhage with amyloidosis-Dutch type more prone to rupture and obstruction, leading to hemorrhages and infarcts. Studying the effects of altered amyloid β metabolism due to mutations like the ‘Dutch’ provides us with a better understanding of amyloid β toxicity, also in other amyloid β diseases like sporadic cerebral amyloid angiopathy and Alzheimer’s disease.

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Familial cerebral amyloid angiopathy presenting as recurrent cerebral haemorrhage

Cited by 147 publications

References 14 publications

Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C).

Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C).

Migraine comorbidity: from genotype to phenotype

Amyloid β in hereditary cerebral hemorrhage with amyloidosis-Dutch type

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