Denser brain capillary network with preserved pericytes in Alzheimer's disease

Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS homeostasis by regulating blood–brain barrier function and cerebral blood flow. It has been suggested that pericytes are lost in Alzheimer�...

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Veröffentlicht in:	Brain pathology (Zurich, Switzerland) Jg. 30; H. 6; S. 1071 - 1086
Hauptverfasser:	Fernandez‐Klett, Francisco, Brandt, Lasse, Fernández‐Zapata, Camila, Abuelnor, Basim, Middeldorp, Jinte, Sluijs, Jacqueline A., Curtis, Maurice, Faull, Richard, Harris, Laura W., Bahn, Sabine, Hol, Elly M., Priller, Josef
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Switzerland John Wiley & Sons, Inc 01.11.2020 John Wiley and Sons Inc
Schlagworte:	Aged Aged, 80 and over Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease Alzheimer's disease (AD) Amyloid Amyloid beta-Peptides - metabolism angiogenesis Blood flow Blood-brain barrier Blood-Brain Barrier - metabolism Blood-Brain Barrier - pathology blood–brain barrier (BBB) Brain Capillaries Capillaries - metabolism Capillaries - pathology Central nervous system Cerebral blood flow Cerebrovascular Circulation - physiology clarity Cortex (frontal) Female Frontal Lobe - metabolism Frontal Lobe - pathology Homeostasis Humans Male Middle Aged Morphometry Neurodegenerative diseases Neuroimaging Pathology Peptide Fragments - metabolism Pericytes Pericytes - metabolism Pericytes - pathology Photons stereology two‐photon microscopy blood-brain barrier (BBB) clarity angiogenesis capillaries pericytes stereology Alzheimer's disease (AD) two-photon microscopy
ISSN:	1015-6305, 1750-3639, 1750-3639
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Abstract	Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS homeostasis by regulating blood–brain barrier function and cerebral blood flow. It has been suggested that pericytes are lost in Alzheimer's disease (AD), implicating this cell type in disease pathology. Here, we have employed state‐of‐the‐art stereological morphometry techniques as well as tissue clearing and two‐photon imaging to assess the distribution of pericytes in two independent cohorts of AD (n = 16 and 13) and non‐demented controls (n = 16 and 4). Stereological quantification revealed increased capillary density with a normal pericyte population in the frontal cortex of AD brains, a region with early amyloid β deposition. Two‐photon analysis of cleared frontal cortex tissue confirmed the preservation of pericytes in AD cases. These results suggest that pericyte demise is not a general hallmark of AD pathology.
AbstractList	Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS homeostasis by regulating blood-brain barrier function and cerebral blood flow. It has been suggested that pericytes are lost in Alzheimer's disease (AD), implicating this cell type in disease pathology. Here, we have employed state-of-the-art stereological morphometry techniques as well as tissue clearing and two-photon imaging to assess the distribution of pericytes in two independent cohorts of AD (n = 16 and 13) and non-demented controls (n = 16 and 4). Stereological quantification revealed increased capillary density with a normal pericyte population in the frontal cortex of AD brains, a region with early amyloid β deposition. Two-photon analysis of cleared frontal cortex tissue confirmed the preservation of pericytes in AD cases. These results suggest that pericyte demise is not a general hallmark of AD pathology. Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS homeostasis by regulating blood-brain barrier function and cerebral blood flow. It has been suggested that pericytes are lost in Alzheimer's disease (AD), implicating this cell type in disease pathology. Here, we have employed state-of-the-art stereological morphometry techniques as well as tissue clearing and two-photon imaging to assess the distribution of pericytes in two independent cohorts of AD (n = 16 and 13) and non-demented controls (n = 16 and 4). Stereological quantification revealed increased capillary density with a normal pericyte population in the frontal cortex of AD brains, a region with early amyloid β deposition. Two-photon analysis of cleared frontal cortex tissue confirmed the preservation of pericytes in AD cases. These results suggest that pericyte demise is not a general hallmark of AD pathology.Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS homeostasis by regulating blood-brain barrier function and cerebral blood flow. It has been suggested that pericytes are lost in Alzheimer's disease (AD), implicating this cell type in disease pathology. Here, we have employed state-of-the-art stereological morphometry techniques as well as tissue clearing and two-photon imaging to assess the distribution of pericytes in two independent cohorts of AD (n = 16 and 13) and non-demented controls (n = 16 and 4). Stereological quantification revealed increased capillary density with a normal pericyte population in the frontal cortex of AD brains, a region with early amyloid β deposition. Two-photon analysis of cleared frontal cortex tissue confirmed the preservation of pericytes in AD cases. These results suggest that pericyte demise is not a general hallmark of AD pathology. Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS homeostasis by regulating blood–brain barrier function and cerebral blood flow. It has been suggested that pericytes are lost in Alzheimer's disease (AD), implicating this cell type in disease pathology. Here, we have employed state‐of‐the‐art stereological morphometry techniques as well as tissue clearing and two‐photon imaging to assess the distribution of pericytes in two independent cohorts of AD (n = 16 and 13) and non‐demented controls (n = 16 and 4). Stereological quantification revealed increased capillary density with a normal pericyte population in the frontal cortex of AD brains, a region with early amyloid β deposition. Two‐photon analysis of cleared frontal cortex tissue confirmed the preservation of pericytes in AD cases. These results suggest that pericyte demise is not a general hallmark of AD pathology.
Author	Abuelnor, Basim Bahn, Sabine Priller, Josef Middeldorp, Jinte Faull, Richard Harris, Laura W. Hol, Elly M. Fernandez‐Klett, Francisco Brandt, Lasse Curtis, Maurice Sluijs, Jacqueline A. Fernández‐Zapata, Camila
AuthorAffiliation	3 Department of Psychiatry and Psychotherapy Charité − Universitätsmedizin Berlin Berlin Germany 1 Laboratory of Molecular Psychiatry Department of Neuropsychiatry Charité − Universitätsmedizin Berlin Berlin Germany 8 University of Edinburgh and UK DRI Edinburgh UK 6 Department of Chemical Engineering and Biotechnology University of Cambridge Cambridge UK 2 Institute for Pathology Universitätsklinik Halle Halle Germany 4 Department of Translational Neuroscience University Medical Center Utrecht Brain Center Utrecht University Utrecht The Netherlands 7 DZNE and BIH Berlin Germany 5 The New Zealand Neurological Foundation Human Brain Bank Centre for Brain Research University of Auckland Auckland New Zealand
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Keywords	blood-brain barrier (BBB) clarity angiogenesis capillaries pericytes stereology Alzheimer's disease (AD) two-photon microscopy
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Snippet	Pericytes are vascular mural cells that surround capillaries of the central nervous system (CNS). They are crucial for brain development and contribute to CNS...
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SubjectTerms	Aged Aged, 80 and over Alzheimer Disease - metabolism Alzheimer Disease - pathology Alzheimer's disease Alzheimer's disease (AD) Amyloid Amyloid beta-Peptides - metabolism angiogenesis Blood flow Blood-brain barrier Blood-Brain Barrier - metabolism Blood-Brain Barrier - pathology blood–brain barrier (BBB) Brain Capillaries Capillaries - metabolism Capillaries - pathology Central nervous system Cerebral blood flow Cerebrovascular Circulation - physiology clarity Cortex (frontal) Female Frontal Lobe - metabolism Frontal Lobe - pathology Homeostasis Humans Male Middle Aged Morphometry Neurodegenerative diseases Neuroimaging Pathology Peptide Fragments - metabolism Pericytes Pericytes - metabolism Pericytes - pathology Photons stereology two‐photon microscopy
Title	Denser brain capillary network with preserved pericytes in Alzheimer's disease
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