American journal of neurodegenerative disease, 2014
In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CA... more In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers. The scoring scheme and choice of staining methods were refined by open-forum discussion. The agreed protocol scored parenchymal and meningeal CAA on a 0-3 scale, capillary CAA as present/absent and vasculopathy on 0-2 scale, in the 4 cortical lobes that were scored separately. A further assessment involving three centres was then undertaken. Neuropathologists in three centres (Bristol, Oxford and Sheffield) independently scored sections from 75 cases (25 from each...
Background: Trigeminal nerve root entry zone demyelination has been implicated as a cause of trig... more Background: Trigeminal nerve root entry zone demyelination has been implicated as a cause of trigeminal neuralgia (TN) in multiple sclerosis (MS) and patients with nerve root vascular compression. We have examined the relationship between pathology and treatment outcome in patients with and without MS, treated for intractable TN by partial sensory rhizotomy (PSR). Methods: We reviewed the operative records, electron microscopic biopsy findings and post-operative satisfaction and pain scores of 23 MS and 47 non-MS patients who underwent PSR between 1992 and 2004. Results: The MS and non-MS patients had similar ages of onset of TN, duration of symptoms, age at surgery and proportions with typical and atypical symptoms. Demyelination was present in 16 MS and 23 nonMS patients (p = 0.129), and a compressing vessel in 5 MS and 23 non-MS patients (p = 0.039). Of those with demyelination, vascular compression was documented in 3 MS and 15 non-MS patients (p = 0.008). Pain and satisfaction ...
Correspondence: Dr Seth Love, Department of Neuropathology, Institute of Clinical Neurosciences, ... more Correspondence: Dr Seth Love, Department of Neuropathology, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol BS16 1LE E-mail: seth.love@bris.ac.uk Departments of Neurology and Neuropathology, Institute of Clinical Neurosciences, University of Bristol, Frenchay Hospital, Bristol, Department of Cellular Pathology, Division of Neuropathology, Southampton General Hospital, Southampton, Department of Neuropathology, Newcastle General Hospital, Department of Neurology, Royal Victoria Infirmary, Newcastle-upon-Tyne, Department of Histopathology, Derriford Hospital, Plymouth, Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, Division of Molecular Histopathology, Addenbrooke’s NHS Trust, Cambridge, UK, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA, USA and Service d’Anatomie et Cytologie Pathologiques, Hôpital Lariboisière, Paris, France
We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which sh... more We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson's disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case. All three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural ...
COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show ev... more COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show evidence of central nervous system (CNS) damage, predominantly ischaemic, in some cases haemorrhagic and occasionally encephalitic. It is unclear how much of the ischaemic damage is mediated by direct or inflammatory effects of virus on the CNS vasculature and how much is secondary to extracranial cardiorespiratory disease. Limited data suggest that the causative SARS-CoV-2 virus may enter the CNS via the nasal mucosa and olfactory fibres, or by haematogenous spread, and is capable of infecting endothelial cells, pericytes and probably neurons. Extracranially, SARS-CoV-2 targets endothelial cells and pericytes, causing endothelial cell dysfunction, vascular leakage and immune activation, sometimes leading to disseminated intravascular coagulation. It remains to be confirmed whether endothelial cells and pericytes in the cerebral vasculature are similarly targeted. Several aspects of COVID-...
Clinical studies indicate that systemic infections accelerate cognitive decline in Alzheimer'... more Clinical studies indicate that systemic infections accelerate cognitive decline in Alzheimer's disease. Animal models suggest that this may be due to enhanced pro-inflammatory changes in the brain. We have performed a post-mortem human study to determine whether systemic infection modifies the neuropathology and in particular, neuroinflammation, in the late-stage of the disease.Sections of cerebral cortex and underlying white matter from controls and Alzheimer's patients who died with or without a terminal systemic infection were immunolabelled and quantified for: (i) Αβ and phosphorylated-tau; (ii) the inflammation-related proteins Iba1, CD68, HLA-DR, FcγRs (CD64, CD32a, CD32b, CD16), CHIL3L1, IL4R and CCR2; and (iii) T-cell marker CD3. In Alzheimer's disease, the synaptic proteins synaptophysin and PSD-95 were quantified by ELISA, and the inflammatory proteins and mRNAs by MesoScale Discovery Multiplex Assays and qPCR, respectively.Systemic infection in Alzheimer's...
Brain pathology (Zurich, Switzerland), Jan 13, 2017
Aβ immunisation of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) tri... more Aβ immunisation of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ immunisation, we have assessed the impact of previous Aβ immunisation on the expression of a range of apoptotic proteins in post-mortem human brain tissue. Cortex from 13 AD patients immunised with AN1792 (iAD) and from 27 non-immunised AD (cAD) cases was immunolabelled for pro-apoptotic proteins implicated in AD pathophysiology: phosphorylated c-Jun N-terminal kinase (pJNK), activated caspase3 (a-casp3), phosphorylated GSK3β on tyrosine 216 (GSK3βtyr216 ), p53 and Cdk5/p35. Expression of these proteins was analysed in relation to immunisation status and other clinical data. The antigen load of all of these pro-apoptotic proteins was significantly lower in iAD than cAD (p < 0.0001). In cAD, significant correlations (p < 0.001) ...
Defects in motor protein-mediated neuronal transport mechanisms have been implicated in a number ... more Defects in motor protein-mediated neuronal transport mechanisms have been implicated in a number of neurodegenerative disorders but remain relatively little studied in Alzheimer's disease (AD). Our aim in the present study was to assess the expression of the anterograde kinesin superfamily motor proteins KIF5A, KIF1B, and KIF21B, and to examine their relationship to levels of hyperphosphorylated tau, amyloid-β protein precursor (AβPP), and amyloid-β (Aβ) in human brain tissue. We used a combination of qPCR, immunoblotting, and ELISA to perform these analyses in midfrontal cortex from 49 AD and 46 control brains. Expression of KIF5A, KIF1B, and KIF21B at gene and protein level was significantly increased in AD. KIF5A protein expression correlated inversely with the levels of AβPP and soluble Aβ in AD brains. Upregulation of KIFs may be an adaptive response to impaired axonal transport in AD.
Glutamate is the major excitatory neurotransmitter of the central nervous system, with the branch... more Glutamate is the major excitatory neurotransmitter of the central nervous system, with the branched-chain amino acids (BCAAs) acting as key nitrogen donors for de novo glutamate synthesis. Despite the importance of these major metabolites, their metabolic pathway in the human brain is still not well characterised. The metabolic pathways that influence the metabolism of BCAAs have been well characterised in rat models. However, the expression of key proteins such as the branched-chain α-ketoacid dehydrogenase (BCKD) complex and glutamate dehydrogenase isozymes (GDH) in the human brain is still not well characterised. We have used specific antibodies to these proteins to analyse their distribution within the human brain and report, for the first time, that the E1α subunit of the BCKD is located in both neurons and vascular endothelial cells. We also demonstrate that GDH is localised to astrocytes, although vascular immunolabelling does occur. The labelling of GDH was most intense in a...
Forensic science, medicine, and pathology, Mar 25, 2017
Central pontine myelinolysis (CPM) is a neurological demyelinating disease of the pons. Although ... more Central pontine myelinolysis (CPM) is a neurological demyelinating disease of the pons. Although usually associated with rapid correction of hyponatremia, CPM may occur despite normonatremia, is often associated with chronic alcoholism and may be asymptomatic. Histological confirmation of asymptomatic CPM is rare. We describe an unusual post-mortem case of extensive but asymptomatic CPM in a chronic alcoholic patient with normonatremia. The affected part of the pons contained thinly myelinated axons with appearances supporting remyelination. We suggest that remyelination may account for the subclinical nature of this patient's CPM.
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. Despite upregulation of ... more Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. Despite upregulation of VEGF in the brain in Alzheimer's disease (AD), probably in response to amyloid-β, vasoconstriction, and tissue hypoxia, there is no consequent increase in microvessel density. VEGF binds to and activates VEGF receptor 2 (VEGFR2), but also binds to VEGF receptor 1 (VEGFR1), which exists in less-active membrane-bound and inactive soluble (sVEGFR1) forms and inhibits pro-angiogenic signaling. We have investigated whether altered expression of VEGF receptors might account for the lack of angiogenic response to VEGF in AD. We assessed the cellular distribution and protein level of VEGFR1 and VEGFR2 in parietal cortex from 50 AD and 36 age-matched control brains, and related the findings to measurements of VEGF and von Willebrand factor level (a marker of microvessel density) in the same tissue samples. VEGFR2 was expressed by neurons, astrocytes and endothelial cells. VEGFR1 was expressed...
Alzheimer's & dementia : the journal of the Alzheimer's Association, Jan 19, 2017
Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered... more Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. The VICCCS-2 suggests standardized use of the National Institute of Neurological ...
Recent studies implicate loss of pericytes in hypoperfusion and blood–brain barrier (BBB) leakage... more Recent studies implicate loss of pericytes in hypoperfusion and blood–brain barrier (BBB) leakage in Alzheimer's disease (AD). In this study, we have measured levels of the pericyte marker, platelet-derived growth factor receptor-β (PDGFRB), and fibrinogen (to assess blood–brain barrier leakage), and analyzed their relationship to indicators of microvessel density (von Willebrand factor level), ante-mortem oxygenation (myelin-associated glycoprotein:proteolipid protein-1 ratio and vascular endothelial growth factor level), Aβ level and plaque load, in precuneus and underlying white matter from 49 AD to 37 control brains. There was reduction in PDGFRB and increased fibrinogen in the precuneus in AD. These changes correlated with reduction in oxygenation and with plaque load. In the underlying white matter, increased fibrinogen correlated with reduced oxygenation, but PDGFRB level was unchanged. The level of platelet-derived growth factor-ββ (PDGF-BB), important for pericyte maint...
American journal of neurodegenerative disease, 2014
In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CA... more In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers. The scoring scheme and choice of staining methods were refined by open-forum discussion. The agreed protocol scored parenchymal and meningeal CAA on a 0-3 scale, capillary CAA as present/absent and vasculopathy on 0-2 scale, in the 4 cortical lobes that were scored separately. A further assessment involving three centres was then undertaken. Neuropathologists in three centres (Bristol, Oxford and Sheffield) independently scored sections from 75 cases (25 from each...
Background: Trigeminal nerve root entry zone demyelination has been implicated as a cause of trig... more Background: Trigeminal nerve root entry zone demyelination has been implicated as a cause of trigeminal neuralgia (TN) in multiple sclerosis (MS) and patients with nerve root vascular compression. We have examined the relationship between pathology and treatment outcome in patients with and without MS, treated for intractable TN by partial sensory rhizotomy (PSR). Methods: We reviewed the operative records, electron microscopic biopsy findings and post-operative satisfaction and pain scores of 23 MS and 47 non-MS patients who underwent PSR between 1992 and 2004. Results: The MS and non-MS patients had similar ages of onset of TN, duration of symptoms, age at surgery and proportions with typical and atypical symptoms. Demyelination was present in 16 MS and 23 nonMS patients (p = 0.129), and a compressing vessel in 5 MS and 23 non-MS patients (p = 0.039). Of those with demyelination, vascular compression was documented in 3 MS and 15 non-MS patients (p = 0.008). Pain and satisfaction ...
Correspondence: Dr Seth Love, Department of Neuropathology, Institute of Clinical Neurosciences, ... more Correspondence: Dr Seth Love, Department of Neuropathology, Institute of Clinical Neurosciences, Frenchay Hospital, Bristol BS16 1LE E-mail: seth.love@bris.ac.uk Departments of Neurology and Neuropathology, Institute of Clinical Neurosciences, University of Bristol, Frenchay Hospital, Bristol, Department of Cellular Pathology, Division of Neuropathology, Southampton General Hospital, Southampton, Department of Neuropathology, Newcastle General Hospital, Department of Neurology, Royal Victoria Infirmary, Newcastle-upon-Tyne, Department of Histopathology, Derriford Hospital, Plymouth, Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, Division of Molecular Histopathology, Addenbrooke’s NHS Trust, Cambridge, UK, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA, USA and Service d’Anatomie et Cytologie Pathologiques, Hôpital Lariboisière, Paris, France
We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which sh... more We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson's disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case. All three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural ...
COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show ev... more COVID-19 is primarily a respiratory disease but up to two thirds of hospitalised patients show evidence of central nervous system (CNS) damage, predominantly ischaemic, in some cases haemorrhagic and occasionally encephalitic. It is unclear how much of the ischaemic damage is mediated by direct or inflammatory effects of virus on the CNS vasculature and how much is secondary to extracranial cardiorespiratory disease. Limited data suggest that the causative SARS-CoV-2 virus may enter the CNS via the nasal mucosa and olfactory fibres, or by haematogenous spread, and is capable of infecting endothelial cells, pericytes and probably neurons. Extracranially, SARS-CoV-2 targets endothelial cells and pericytes, causing endothelial cell dysfunction, vascular leakage and immune activation, sometimes leading to disseminated intravascular coagulation. It remains to be confirmed whether endothelial cells and pericytes in the cerebral vasculature are similarly targeted. Several aspects of COVID-...
Clinical studies indicate that systemic infections accelerate cognitive decline in Alzheimer'... more Clinical studies indicate that systemic infections accelerate cognitive decline in Alzheimer's disease. Animal models suggest that this may be due to enhanced pro-inflammatory changes in the brain. We have performed a post-mortem human study to determine whether systemic infection modifies the neuropathology and in particular, neuroinflammation, in the late-stage of the disease.Sections of cerebral cortex and underlying white matter from controls and Alzheimer's patients who died with or without a terminal systemic infection were immunolabelled and quantified for: (i) Αβ and phosphorylated-tau; (ii) the inflammation-related proteins Iba1, CD68, HLA-DR, FcγRs (CD64, CD32a, CD32b, CD16), CHIL3L1, IL4R and CCR2; and (iii) T-cell marker CD3. In Alzheimer's disease, the synaptic proteins synaptophysin and PSD-95 were quantified by ELISA, and the inflammatory proteins and mRNAs by MesoScale Discovery Multiplex Assays and qPCR, respectively.Systemic infection in Alzheimer's...
Brain pathology (Zurich, Switzerland), Jan 13, 2017
Aβ immunisation of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) tri... more Aβ immunisation of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ immunisation, we have assessed the impact of previous Aβ immunisation on the expression of a range of apoptotic proteins in post-mortem human brain tissue. Cortex from 13 AD patients immunised with AN1792 (iAD) and from 27 non-immunised AD (cAD) cases was immunolabelled for pro-apoptotic proteins implicated in AD pathophysiology: phosphorylated c-Jun N-terminal kinase (pJNK), activated caspase3 (a-casp3), phosphorylated GSK3β on tyrosine 216 (GSK3βtyr216 ), p53 and Cdk5/p35. Expression of these proteins was analysed in relation to immunisation status and other clinical data. The antigen load of all of these pro-apoptotic proteins was significantly lower in iAD than cAD (p < 0.0001). In cAD, significant correlations (p < 0.001) ...
Defects in motor protein-mediated neuronal transport mechanisms have been implicated in a number ... more Defects in motor protein-mediated neuronal transport mechanisms have been implicated in a number of neurodegenerative disorders but remain relatively little studied in Alzheimer's disease (AD). Our aim in the present study was to assess the expression of the anterograde kinesin superfamily motor proteins KIF5A, KIF1B, and KIF21B, and to examine their relationship to levels of hyperphosphorylated tau, amyloid-β protein precursor (AβPP), and amyloid-β (Aβ) in human brain tissue. We used a combination of qPCR, immunoblotting, and ELISA to perform these analyses in midfrontal cortex from 49 AD and 46 control brains. Expression of KIF5A, KIF1B, and KIF21B at gene and protein level was significantly increased in AD. KIF5A protein expression correlated inversely with the levels of AβPP and soluble Aβ in AD brains. Upregulation of KIFs may be an adaptive response to impaired axonal transport in AD.
Glutamate is the major excitatory neurotransmitter of the central nervous system, with the branch... more Glutamate is the major excitatory neurotransmitter of the central nervous system, with the branched-chain amino acids (BCAAs) acting as key nitrogen donors for de novo glutamate synthesis. Despite the importance of these major metabolites, their metabolic pathway in the human brain is still not well characterised. The metabolic pathways that influence the metabolism of BCAAs have been well characterised in rat models. However, the expression of key proteins such as the branched-chain α-ketoacid dehydrogenase (BCKD) complex and glutamate dehydrogenase isozymes (GDH) in the human brain is still not well characterised. We have used specific antibodies to these proteins to analyse their distribution within the human brain and report, for the first time, that the E1α subunit of the BCKD is located in both neurons and vascular endothelial cells. We also demonstrate that GDH is localised to astrocytes, although vascular immunolabelling does occur. The labelling of GDH was most intense in a...
Forensic science, medicine, and pathology, Mar 25, 2017
Central pontine myelinolysis (CPM) is a neurological demyelinating disease of the pons. Although ... more Central pontine myelinolysis (CPM) is a neurological demyelinating disease of the pons. Although usually associated with rapid correction of hyponatremia, CPM may occur despite normonatremia, is often associated with chronic alcoholism and may be asymptomatic. Histological confirmation of asymptomatic CPM is rare. We describe an unusual post-mortem case of extensive but asymptomatic CPM in a chronic alcoholic patient with normonatremia. The affected part of the pons contained thinly myelinated axons with appearances supporting remyelination. We suggest that remyelination may account for the subclinical nature of this patient's CPM.
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. Despite upregulation of ... more Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. Despite upregulation of VEGF in the brain in Alzheimer's disease (AD), probably in response to amyloid-β, vasoconstriction, and tissue hypoxia, there is no consequent increase in microvessel density. VEGF binds to and activates VEGF receptor 2 (VEGFR2), but also binds to VEGF receptor 1 (VEGFR1), which exists in less-active membrane-bound and inactive soluble (sVEGFR1) forms and inhibits pro-angiogenic signaling. We have investigated whether altered expression of VEGF receptors might account for the lack of angiogenic response to VEGF in AD. We assessed the cellular distribution and protein level of VEGFR1 and VEGFR2 in parietal cortex from 50 AD and 36 age-matched control brains, and related the findings to measurements of VEGF and von Willebrand factor level (a marker of microvessel density) in the same tissue samples. VEGFR2 was expressed by neurons, astrocytes and endothelial cells. VEGFR1 was expressed...
Alzheimer's & dementia : the journal of the Alzheimer's Association, Jan 19, 2017
Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered... more Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. The VICCCS-2 suggests standardized use of the National Institute of Neurological ...
Recent studies implicate loss of pericytes in hypoperfusion and blood–brain barrier (BBB) leakage... more Recent studies implicate loss of pericytes in hypoperfusion and blood–brain barrier (BBB) leakage in Alzheimer's disease (AD). In this study, we have measured levels of the pericyte marker, platelet-derived growth factor receptor-β (PDGFRB), and fibrinogen (to assess blood–brain barrier leakage), and analyzed their relationship to indicators of microvessel density (von Willebrand factor level), ante-mortem oxygenation (myelin-associated glycoprotein:proteolipid protein-1 ratio and vascular endothelial growth factor level), Aβ level and plaque load, in precuneus and underlying white matter from 49 AD to 37 control brains. There was reduction in PDGFRB and increased fibrinogen in the precuneus in AD. These changes correlated with reduction in oxygenation and with plaque load. In the underlying white matter, increased fibrinogen correlated with reduced oxygenation, but PDGFRB level was unchanged. The level of platelet-derived growth factor-ββ (PDGF-BB), important for pericyte maint...
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