Senile dementia associated with amyloid β protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-ε4 allele

Ruben Vidal, Miguel Calero, Pedro Piccardo, Martin Farlow, Frederick Unverzagt, Enrique Méndez, Adolfo Jiménez-Huete, Ronald Beavis, Gloria Gallo, Estrella Gomez-Tortosa, Jorge Ghiso, Bradley T. Hyman, Blas Frangione, Bernardino Ghetti

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Abstract

Amyloid β protein deposition in cortical and leptomeningeal vessels, causing the most common type of cerebral amyloid angiopathy, is found in sporadic and familial Alzheimer's disease (AD) and is the principal feature in the hereditary cerebral hemorrhage with amyloidosis, Dutch type. The presence of the Apolipoprotein E (APOE)-ε4 allele has been implicated as a risk factor for AD and the development of cerebral amyloid angiopathy in AD. We report clinical, pathological and biochemical studies on two APOE-ε4 homozygous subjects, who had senile dementia and whose main neuropathological feature was a severe and diffuse amyloid angiopathy associated with perivascular tau neurofibrillary pathology. Amyloid β protein and ApoE immunoreactivity were observed in leptomeningeal vessels as well as in medium-sized and small vessels and capillaries in the parenchyma of the neocortex, hippocampus, thalamus, cerebellum, midbrain, pons, and medulla. The predominant peptide form of amyloid β protein was that terminating at residue Val40, as determined by immunohistochemistry, amino acid sequence and mass spectrometry analysis. A crown of tau-immunopositive cell processes was consistently present around blood vessels. DNA sequence analysis of the Amyloid Precursor Protein gene and Presenilin-1 (PS-1) gene revealed no mutations. In these APOE-ε4 homozygous patients, the pathological process differed from that typically seen in AD in that they showed a heavy burden of perivascular tau-immunopositive cell processes associated with severe amyloid β protein angiopathy, neurofibrillary tangles, some cortical Lewy bodies and an absence of neuritic plaques. These cases emphasize the concept that tau deposits may be pathogenetically related to amyloid β protein deposition.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalActa Neuropathologica
Volume100
Issue number1
DOIs
StatePublished - Jul 2000

Fingerprint

Apolipoprotein E4
Amyloidogenic Proteins
Amyloid Plaques
Alzheimer Disease
Alleles
Pathology
Cerebral Amyloid Angiopathy
Presenilin-1
Lewy Bodies
Neurofibrillary Tangles
Pons
Amyloid beta-Protein Precursor
Neocortex
Apolipoproteins E
Pathologic Processes
Mesencephalon
Crowns
Thalamus
DNA Sequence Analysis
Cerebellum

Keywords

  • Alzheimer's disease
  • Amyloid β protein
  • Cerebral amyloid angiopathy
  • Neurofibrillary tangles
  • Senile plaques

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Senile dementia associated with amyloid β protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-ε4 allele. / Vidal, Ruben; Calero, Miguel; Piccardo, Pedro; Farlow, Martin; Unverzagt, Frederick; Méndez, Enrique; Jiménez-Huete, Adolfo; Beavis, Ronald; Gallo, Gloria; Gomez-Tortosa, Estrella; Ghiso, Jorge; Hyman, Bradley T.; Frangione, Blas; Ghetti, Bernardino.

In: Acta Neuropathologica, Vol. 100, No. 1, 07.2000, p. 1-12.

Research output: Contribution to journalArticle

Vidal, Ruben ; Calero, Miguel ; Piccardo, Pedro ; Farlow, Martin ; Unverzagt, Frederick ; Méndez, Enrique ; Jiménez-Huete, Adolfo ; Beavis, Ronald ; Gallo, Gloria ; Gomez-Tortosa, Estrella ; Ghiso, Jorge ; Hyman, Bradley T. ; Frangione, Blas ; Ghetti, Bernardino. / Senile dementia associated with amyloid β protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-ε4 allele. In: Acta Neuropathologica. 2000 ; Vol. 100, No. 1. pp. 1-12.
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AU - Farlow, Martin

AU - Unverzagt, Frederick

AU - Méndez, Enrique

AU - Jiménez-Huete, Adolfo

AU - Beavis, Ronald

AU - Gallo, Gloria

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AB - Amyloid β protein deposition in cortical and leptomeningeal vessels, causing the most common type of cerebral amyloid angiopathy, is found in sporadic and familial Alzheimer's disease (AD) and is the principal feature in the hereditary cerebral hemorrhage with amyloidosis, Dutch type. The presence of the Apolipoprotein E (APOE)-ε4 allele has been implicated as a risk factor for AD and the development of cerebral amyloid angiopathy in AD. We report clinical, pathological and biochemical studies on two APOE-ε4 homozygous subjects, who had senile dementia and whose main neuropathological feature was a severe and diffuse amyloid angiopathy associated with perivascular tau neurofibrillary pathology. Amyloid β protein and ApoE immunoreactivity were observed in leptomeningeal vessels as well as in medium-sized and small vessels and capillaries in the parenchyma of the neocortex, hippocampus, thalamus, cerebellum, midbrain, pons, and medulla. The predominant peptide form of amyloid β protein was that terminating at residue Val40, as determined by immunohistochemistry, amino acid sequence and mass spectrometry analysis. A crown of tau-immunopositive cell processes was consistently present around blood vessels. DNA sequence analysis of the Amyloid Precursor Protein gene and Presenilin-1 (PS-1) gene revealed no mutations. In these APOE-ε4 homozygous patients, the pathological process differed from that typically seen in AD in that they showed a heavy burden of perivascular tau-immunopositive cell processes associated with severe amyloid β protein angiopathy, neurofibrillary tangles, some cortical Lewy bodies and an absence of neuritic plaques. These cases emphasize the concept that tau deposits may be pathogenetically related to amyloid β protein deposition.

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