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Vascular and Nonvascular Mechanisms of Cognitive Impairment and Dementia

  • Betul Kara
    Affiliations
    Department of Translational Neuroscience, Michigan State University, 400 Monroe Avenue Northwest, Grand Rapids, MI 49503, USA
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  • Marcia N. Gordon
    Affiliations
    Department of Translational Neuroscience, Michigan State University, 400 Monroe Avenue Northwest, Grand Rapids, MI 49503, USA
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  • Mahsa Gifani
    Affiliations
    Department of Translational Neuroscience, Michigan State University, 400 Monroe Avenue Northwest, Grand Rapids, MI 49503, USA
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  • Anne M. Dorrance
    Affiliations
    Department of Pharmacology and Toxicology, Michigan State University, 1355 Bogue Street, East Lansing, MI 48824, USA
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  • Scott E. Counts
    Correspondence
    Corresponding author. Department of Translational Neuroscience, College of Human Medicine, Michigan State University, 400 Monroe Avenue Northwest, Grand Rapids, MI 49503.
    Affiliations
    Department of Translational Neuroscience, Michigan State University, 400 Monroe Avenue Northwest, Grand Rapids, MI 49503, USA

    Department of Family Medicine, Michigan State University, 15 Michigan Street Northeast, Grand Rapids, MI 49503, USA

    Hauenstein Neurosciences Center, Mercy Health Saint Mary’s Medical Center, 20 Jefferson Avenue Southeast, Grand Rapids, MI 49503, USA
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Published:October 18, 2022DOI:https://doi.org/10.1016/j.cger.2022.07.006

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      References

        • Hinz F.I.
        • Geschwind D.H.
        Molecular genetics of neurodegenerative dementias.
        Cold Spring Harbor Perspect Biol. 2017; 9: a023705
        • Bird T.D.
        Genetic aspects of Alzheimer disease.
        Genet Med. 2008; 10: 231-239
        • Genin E.
        • Hannequin D.
        • Wallon D.
        • et al.
        APOE and Alzheimer disease: a major gene with semi-dominant inheritance.
        Mol Psychiatry. 2011; 16: 903-907
        • Lambert J.C.
        • Heath S.
        • Even G.
        • et al.
        Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease.
        Nat Genet. 2009; 41: 1094-1099
        • Hollingworth P.
        • Harold D.
        • Sims R.
        • et al.
        Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.
        Nat Genet. 2011; 43: 429-435
        • Rademakers R.
        • Neumann M.
        • Mackenzie I.R.
        Advances in understanding the molecular basis of frontotemporal dementia.
        Nat Rev Neurol. 2012; 8: 423-434
        • Van Mossevelde S.
        • Engelborghs S.
        • van der Zee J.
        • et al.
        Genotype-phenotype links in frontotemporal lobar degeneration.
        Nat Rev Neurol. 2018; 14: 363-378
        • de Majo M.T.S.
        • Smith B.N.
        • Nishimura A.L.
        • et al.
        ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase function.
        Neurobiol Aging. 2018; 7: 266.e1-266.e10
        • Bernardi L.
        • Tomaino C.
        • Anfossi M.
        • et al.
        Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia.
        Neurobiol Aging. 2009; 30: 1825-1833
        • Geiger J.T.
        • Ding J.
        • Crain B.
        • et al.
        Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies.
        Neurobiol Dis. 2016; 94: 55-62
        • Kelley B.J.
        • Haidar W.
        • Boeve B.F.
        • et al.
        Alzheimer disease-like phenotype associated with the c.154delA mutation in progranulin.
        Arch Neurol. 2010; 67: 171-177
        • Orme T.
        • Hernandez D.
        • Ross O.A.
        • et al.
        Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies.
        Acta Neuropathol Commun. 2020; 8: 5
        • Mishra A.
        • Ferrari R.
        • Heutink P.
        • et al.
        Gene-based association studies report genetic links for clinical subtypes of frontotemporal dementia.
        Brain. 2017; 140: 1437-1446
        • Tsuang D.
        • Leverenz J.B.
        • Lopez O.L.
        • et al.
        APOE epsilon4 increases risk for dementia in pure synucleinopathies.
        JAMA Neurol. 2013; 70: 223-228
        • Erkkinen M.G.
        • Kim M.O.
        • Geschwind M.D.
        Clinical neurology and epidemiology of the major neurodegenerative diseases.
        Cold Spring Harbor Perspect Biol. 2018; 10: a033118
        • Mizuno T.
        • Mizuta I.
        • Watanabe-Hosomi A.
        • et al.
        Clinical and genetic aspects of CADASIL.
        Front Aging Neurosci. 2020; 12: 91
        • Livingston G.
        • Huntley J.
        • Sommerlad A.
        • et al.
        Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.
        Lancet. 2020; 396: 413-446
        • Iadecola C.
        The pathobiology of vascular dementia.
        Neuron. 2013; 80: 844-866
        • Cortes-Canteli M.
        • Iadecola C.
        Alzheimer's disease and vascular aging: JACC focus seminar.
        J Am Coll Cardiol. 2020; 75: 942-951
        • Iadecola C.
        • Duering M.
        • Hachinski V.
        • et al.
        Vascular cognitive impairment and dementia: JACC scientific expert panel.
        J Am Coll Cardiol. 2019; 73: 3326-3344
        • Skrobot O.A.
        • Black S.E.
        • Chen C.
        • et al.
        Progress toward standardized diagnosis of vascular cognitive impairment: guidelines from the vascular impairment of cognition classification consensus study.
        Alzheimer's Demen. 2018; 14: 280-292
        • Rost N.S.
        • Brodtmann A.
        • Pase M.P.
        • et al.
        Post-stroke cognitive impairment and dementia.
        Circ Res. 2022; 130: 1252-1271
        • Hodis J.D.
        • Gottesman R.F.
        • Windham B.G.
        • et al.
        Association of hypertension according to new american college of cardiology/american heart association blood pressure guidelines with incident dementia in the ARIC study cohort.
        J Am Heart Assoc. 2020; 9: e017546
        • Group SMIftSR
        • Williamson J.D.
        • Pajewski N.M.
        • et al.
        Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial.
        J Am Med Assoc. 2019; 321: 553-561
        • Group SMIftSR
        • Nasrallah I.M.
        • Pajewski N.M.
        • et al.
        Association of intensive vs standard blood pressure control with cerebral white matter lesions.
        J Am Med Assoc. 2019; 322: 524-534
        • Jennings J.R.
        • Muldoon M.F.
        • Ryan C.
        • et al.
        Reduced cerebral blood flow response and compensation among patients with untreated hypertension.
        Neurology. 2005; 64: 1358-1365
        • Longden T.A.
        • Dabertrand F.
        • Koide M.
        • et al.
        Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow.
        Nat Neurosci. 2017; 20: 717-726
        • Koide M.
        • Harraz O.F.
        • Dabertrand F.
        • et al.
        Differential restoration of functional hyperemia by antihypertensive drug classes in hypertension-related cerebral small vessel disease.
        J Clin Invest. 2021; 131: e149029
        • Shih A.Y.
        • Blinder P.
        • Tsai P.S.
        • et al.
        The smallest stroke: occlusion of one penetrating vessel leads to infarction and a cognitive deficit.
        Nat Neurosci. 2013; 16: 55-63
        • Nishimura N.
        • Schaffer C.B.
        • Friedman B.
        • et al.
        Penetrating arterioles are a bottleneck in the perfusion of neocortex.
        Proc Natl Acad Sci U S A. 2007; 104: 365-370
        • Cipolla M.J.
        • Li R.
        • Vitullo L.
        Perivascular innervation of penetrating brain parenchymal arterioles.
        J Cardiovasc Pharmacol. 2004; 44: 1-8
        • Diaz-Otero J.M.
        • Yen T.-C.
        • Ahmad A.
        • et al.
        Transient receptor potential vanilloid 4 channels are important regulators of parenchymal arteriole dilation and cognitive function.
        Microcirculation. 2019; 26: e12535
        • Liu L.
        • Guo M.
        • Lv X.
        • et al.
        Role of transient receptor potential vanilloid 4 in vascular function.
        Front Mol biosciences. 2021; 8: 677661
        • Matin N.
        • Fisher C.
        • Lansdell T.A.
        • et al.
        Soluble epoxide hydrolase inhibition improves cognitive function and parenchymal artery dilation in a hypertensive model of chronic cerebral hypoperfusion.
        Microcirculation. 2021; 28: e12653
        • Griñán-Ferré C.
        • Codony S.
        • Pujol E.
        • et al.
        Pharmacological inhibition of soluble epoxide hydrolase as a new therapy for alzheimer's disease.
        Neurotherapeutics. 2020; 17: 1825-1835
        • Iliff J.J.
        • Wang M.
        • Liao Y.
        • et al.
        A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β.
        Sci translational Med. 2012; 4: 147ra111
        • Morris A.W.
        • Sharp M.M.
        • Albargothy N.J.
        • et al.
        Vascular basement membranes as pathways for the passage of fluid into and out of the brain.
        Acta Neuropathol. 2016; 131: 725-736
        • Mortensen K.N.
        • Sanggaard S.
        • Mestre H.
        • et al.
        Impaired glymphatic transport in spontaneously hypertensive rats.
        J Neurosci. 2019; 39: 6365-6377
        • Dugger B.N.
        • Dickson D.W.
        Pathology of neurodegenerative diseases.
        Cold Spring Harb Perspect Biol. 2017; 9: a028035
        • Matej R.
        • Tesar A.
        • Rusina R.
        Alzheimer's disease and other neurodegenerative dementias in comorbidity: a clinical and neuropathological overview.
        Clin Biochem. 2019; 73: 26-31
        • Mueller R.L.
        • Combs B.
        • Alhadidy M.M.
        • et al.
        Tau: a signaling hub protein.
        Front Mol Neurosci. 2021; 14: 647054
        • Guerrero-Munoz M.J.
        • Gerson J.
        • Castillo-Carranza D.L.
        Tau oligomers: the toxic player at synapses in alzheimer's disease.
        Front Cell Neurosci. 2015; 9: 464
        • Reddy P.H.
        • Oliver D.M.
        Amyloid beta and phosphorylated tau-induced defective autophagy and mitophagy in alzheimer's disease.
        Cells. 2019; 8: 488
        • Mansuroglu Z.
        • Benhelli-Mokrani H.
        • Marcato V.
        • et al.
        Loss of Tau protein affects the structure, transcription and repair of neuronal pericentromeric heterochromatin.
        Sci Rep. 2016; 6: 33047
        • Li S.
        • Jin M.
        • Koeglsperger T.
        • et al.
        Soluble Abeta oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors.
        J Neurosci. 2011; 31: 6627-6638
        • Tolar M.
        • Hey J.
        • Power A.
        • et al.
        Neurotoxic soluble amyloid oligomers drive alzheimer's pathogenesis and represent a clinically validated target for slowing disease progression.
        Int J Mol Sci. 2021; 22: 6355
        • Brito-Moreira J.
        • Paula-Lima A.C.
        • Bomfim T.R.
        • et al.
        Abeta oligomers induce glutamate release from hippocampal neurons.
        Curr Alzheimer Res. 2011; 8: 552-562
        • Vandal M.
        • Bourassa P.
        • Calon F.
        Can insulin signaling pathways be targeted to transport Abeta out of the brain?.
        Front Aging Neurosci. 2015; 7: 114
        • Koga S.
        • Sekiya H.
        • Kondru N.
        • et al.
        Neuropathology and molecular diagnosis of Synucleinopathies.
        Mol neurodegeneration. 2021; 16: 83
        • Jellinger K.A.
        Significance of brain lesions in Parkinson disease dementia and Lewy body dementia.
        Front Neurol Neurosci. 2009; 24: 114-125
        • Choi M.G.
        • Kim M.J.
        • Kim D.G.
        • et al.
        Sequestration of synaptic proteins by alpha-synuclein aggregates leading to neurotoxicity is inhibited by small peptide.
        PLoS One. 2018; 13: e0195339
        • Bernal-Conde L.D.
        • Ramos-Acevedo R.
        • Reyes-Hernandez M.A.
        • et al.
        Alpha-synuclein physiology and pathology: a perspective on cellular structures and organelles.
        Front Neurosci. 2019; 13: 1399
        • Abeliovich A.
        • Schmitz Y.
        • Farinas I.
        • et al.
        Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system.
        Neuron. 2000; 25: 239-252
        • Teixeira M.
        • Sheta R.
        • Idi W.
        • et al.
        Alpha-synuclein and the endolysosomal system in Parkinson's disease: guilty by association.
        Biomolecules. 2021; 11: 1333
        • Keating S.S.
        • San Gil R.
        • Swanson M.E.V.
        • et al.
        TDP-43 pathology: from noxious assembly to therapeutic removal.
        Prog Neurobiol. 2022; 211: 102229
        • Meneses A.
        • Koga S.
        • O'Leary J.
        • et al.
        TDP-43 pathology in alzheimer's disease.
        Mol neurodegeneration. 2021; 16: 84
        • Nelson P.T.
        • Dickson D.W.
        • Trojanowski J.Q.
        • et al.
        Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report.
        Brain. 2019; 142: 1503-1527
        • Prasad A.
        • Bharathi V.
        • Sivalingam V.
        • et al.
        Molecular mechanisms of TDP-43 misfolding and pathology in amyotrophic lateral sclerosis.
        Front Mol Neurosci. 2019; 12: 25
        • Butterfield D.A.
        • Halliwell B.
        Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease.
        Nat Rev Neurosci. 2019; 20: 148-160
        • Galliciotti G.
        • De Jaco A.
        • Sepulveda-Falla D.
        • et al.
        Role of cellular oxidative stress in dementia.
        in: Martin C.R. Preedy V.R. Genetics, neurology, behavior, and diet in dementia: the neuroscience of dementia. Academic Press, Cambridge, MA2020: 147-161 (chap 10)
        • Floyd R.A.
        • Hensley K.
        Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases.
        Neurobiol Aging. 2002; 23: 795-807
        • Kelly S.C.
        • He B.
        • Perez S.E.
        • et al.
        Locus coeruleus cellular and molecular pathology during the progression of Alzheimer's disease.
        Acta Neuropathol Commun. 2017; 5: 8
        • Smith M.A.
        • Nunomura A.
        • Zhu X.
        • et al.
        Metabolic, metallic, and mitotic sources of oxidative stress in Alzheimer disease.
        Antioxid Redox Signal Fall. 2000; 2: 413-420
        • Williams T.I.
        • Lynn B.C.
        • Markesbery W.R.
        • et al.
        Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer's disease.
        Neurobiol Aging. 2005; 27: 1094-1099
        • Kelly S.C.
        • Nelson P.T.
        • Counts S.E.
        Pontine arteriolosclerosis and locus coeruleus oxidative stress differentiate resilience from mild cognitive impairment in a clinical pathologic cohort.
        J Neuropathol Exp Neurol. 2021; 80: 325-335
        • Sharma C.
        • Kim S.R.
        Linking oxidative stress and proteinopathy in alzheimer's disease.
        Antioxidants (Basel). 2021; 10: 1231
        • Martinez A.
        • Carmona M.
        • Portero-Otin M.
        • et al.
        Type-dependent oxidative damage in frontotemporal lobar degeneration: cortical astrocytes are targets of oxidative damage.
        J Neuropathol Exp Neurol. 2008; 67: 1122-1136
        • Esteras N.
        • Rohrer J.D.
        • Hardy J.
        • et al.
        Mitochondrial hyperpolarization in iPSC-derived neurons from patients of FTDP-17 with 10+16 MAPT mutation leads to oxidative stress and neurodegeneration.
        Redox Biol. 2017; 12: 410-422
        • Garcia-Esparcia P.
        • Lopez-Gonzalez I.
        • Grau-Rivera O.
        • et al.
        Dementia with Lewy bodies: molecular pathology in the frontal cortex in typical and rapidly progressive forms.
        Front Neurol. 2017; 8: 89
        • Gomez-Tortosa E.
        • Gonzalo I.
        • Newell K.
        • et al.
        Patterns of protein nitration in dementia with Lewy bodies and striatonigral degeneration.
        Acta Neuropathol. 2002; 103: 495-500
        • Bosco D.A.
        • Fowler D.M.
        • Zhang Q.
        • et al.
        Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate alpha-synuclein fibrilization.
        Nat Chem Biol. 2006; 2: 249-253
        • Finkel T.
        Signal transduction by reactive oxygen species.
        J Cell Biol. 2011; 194: 7-15
        • Wang W.
        • Zhao F.
        • Ma X.
        • et al.
        Mitochondria dysfunction in the pathogenesis of Alzheimer's disease: recent advances.
        Mol neurodegeneration. 2020; 15: 30
        • Beck J.S.
        • Mufson E.J.
        • Counts S.E.
        Evidence for mitochondrial UPR gene activation in familial and sporadic Alzheimer's disease.
        Curr Alzheimer Res. 2015; 13: 610-614
        • Choi D.H.
        • Lee K.H.
        • Kim J.H.
        • et al.
        NADPH oxidase 1, a novel molecular source of ROS in hippocampal neuronal death in vascular dementia.
        Antioxid Redox Signal. 2014; 21: 533-550
        • Sultana R.
        • Piroddi M.
        • Galli F.
        • et al.
        Protein levels and activity of some antioxidant enzymes in hippocampus of subjects with amnestic mild cognitive impairment.
        Neurochem Res. 2008; 33: 2540-2546
        • Rinaldi P.
        • Polidori M.C.
        • Metastasio A.
        • et al.
        Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease.
        Neurobiol Aging. 2003; 24: 915-919
        • Shukla D.
        • Mandal P.K.
        • Tripathi M.
        • et al.
        Quantitation of in vivo brain glutathione conformers in cingulate cortex among age-matched control, MCI, and AD patients using MEGA-PRESS.
        Hum Brain Mapp. 2020; 41: 194-217
        • Tonnies E.
        • Trushina E.
        Oxidative stress, synaptic dysfunction, and alzheimer's disease.
        J Alzheimers Dis. 2017; 57: 1105-1121
        • Uddin M.S.
        • Lim L.W.
        Glial cells in Alzheimer's disease: from neuropathological changes to therapeutic implications.
        Ageing Res Rev. 2022; 78: 101622
        • McGeer P.L.
        • Kawamata T.
        • Walker D.G.
        • et al.
        Microglia in degenerative neurological disease.
        Glia. 1993; 7: 84-92
        • Boraschi D.
        • Italiani P.
        • Weil S.
        • et al.
        The family of the interleukin-1 receptors.
        Immunol Rev. 2018; 281: 197-232
        • Rose-John S.
        Interleukin-6 signalling in health and disease.
        F1000Res. 2020; 9 (Faculty Rev-1013): F1000
        • Gough P.
        • Myles I.A.
        Tumor necrosis factor receptors: pleiotropic signaling complexes and their differential effects.
        Front Immunol. 2020; 11: 585880
        • Andrews S.J.
        • Fulton-Howard B.
        • Goate A.
        Interpretation of risk loci from genome-wide association studies of Alzheimer's disease.
        Lancet Neurol. 2020; 19: 326-335
        • Bellenguez C.
        • Kucukali F.
        • Jansen I.E.
        • et al.
        New insights into the genetic etiology of Alzheimer's disease and related dementias.
        Nat Genet. 2022; 54: 412-436
        • Bright F.
        • Werry E.L.
        • Dobson-Stone C.
        • et al.
        Neuroinflammation in frontotemporal dementia.
        Nat Rev Neurol. 2019; 15: 540-555
        • Amin J.
        • Erskine D.
        • Donaghy P.C.
        • et al.
        Inflammation in dementia with Lewy bodies.
        Neurobiol Dis. 2022; 168: 105698
        • Boche D.
        • Gordon M.N.
        Diversity of transcriptomic microglial phenotypes in aging and Alzheimer's disease.
        Alzheimers Dement. 2022; 18: 360-376
        • Keren-Shaul H.
        • Spinrad A.
        • Weiner A.
        • et al.
        A unique microglia type Associated with restricting development of alzheimer's disease.
        Cell. 2017; 169: 1276-1290 e17
        • Krasemann S.
        • Madore C.
        • Cialic R.
        • et al.
        The TREM2-APOE pathway drives the transcriptional phenotype of dysfunctional microglia in neurodegenerative diseases.
        Immunity. 2017; 47: 566-581
        • Liddelow S.A.
        • Guttenplan K.A.
        • Clarke L.E.
        • et al.
        Neurotoxic reactive astrocytes are induced by activated microglia.
        Nature. 2017; 541: 481-487
        • Salminen A.
        • Ojala J.
        • Kauppinen A.
        • et al.
        Inflammation in Alzheimer's disease: amyloid-beta oligomers trigger innate immunity defence via pattern recognition receptors.
        Prog Neurobiol. 2009; 87: 181-194
        • Mossanen Parsi M.
        • Duval C.
        • Ariens R.A.S.
        Vascular dementia and crosstalk between the complement and coagulation systems.
        Front Cardiovasc Med. 2021; 8: 803169
        • Jiang H.
        • Burdick D.
        • Glabe C.G.
        • et al.
        beta-Amyloid activates complement by binding to a specific region of the collagen-like domain of the C1q A chain.
        J Immunol. 1994; 152: 5050-5059
        • Tenner A.J.
        • Stevens B.
        • Woodruff T.M.
        New tricks for an ancient system: physiological and pathological roles of complement in the CNS.
        Mol Immunol. 2018; 102: 3-13
        • Hong S.
        • Beja-Glasser V.F.
        • Nfonoyim B.M.
        • et al.
        Complement and microglia mediate early synapse loss in Alzheimer mouse models.
        Science. 2016; 352: 712-716
        • Fonseca M.I.
        • Ager R.R.
        • Chu S.H.
        • et al.
        Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease.
        J Immunol. 2009; 183: 1375-1383
        • Shi X.
        • Ohta Y.
        • Liu X.
        • et al.
        Chronic cerebral hypoperfusion activates the coagulation and complement cascades in alzheimer's disease mice.
        Neuroscience. 2019; 416: 126-136
        • Fan R.
        • DeFilippis K.
        • Van Nostrand W.E.
        Induction of complement proteins in a mouse model for cerebral microvascular A beta deposition.
        J neuroinflammation. 2007; 4: 22
        • Schrag M.
        • Kirshner H.
        Neuropsychological effects of cerebral amyloid angiopathy.
        Curr Neurol Neurosci Rep. 2016; 16: 76
        • Bhatia K.
        • Kindelin A.
        • Nadeem M.
        • et al.
        Complement C3a receptor (C3aR) mediates vascular dysfunction, hippocampal pathology, and cognitive impairment in a mouse model of VCID.
        Transl Stroke Res. 2022; https://doi.org/10.1007/s12975-022-00993-x
        • Nixon R.A.
        The role of autophagy in neurodegenerative disease.
        Nat Med. 2013; 19: 983-997
        • Koren 3rd, J.
        • Jinwal U.K.
        • Lee D.C.
        • et al.
        Chaperone signalling complexes in Alzheimer's disease.
        J Cell Mol Med. 2009; 13: 619-630
        • Fahnestock M.
        • Yu G.
        • Coughlin M.D.
        ProNGF: a neurotrophic or an apoptotic molecule?.
        Prog Brain Res. 2004; 146: 107-110
        • Counts S.E.
        • Mufson E.J.
        The role of nerve growth factor receptors in cholinergic basal forebrain degeneration in prodromal Alzheimer disease.
        J Neuropathol Exp Neurol. 2005; 64: 263-272
        • Bernstein A.I.
        • Lin Y.
        • Street R.C.
        • et al.
        5-Hydroxymethylation-associated epigenetic modifiers of Alzheimer's disease modulate Tau-induced neurotoxicity.
        Hum Mol Genet. 2016; 25: 2437-2450
        • Beck J.S.
        • Madaj Z.
        • Cheema C.T.
        • et al.
        Co-expression network analysis of frontal cortex during the progression of alzheimer's disease.
        Cereb Cortex. 2022; : bhac001
        • Verhaar B.J.H.
        • Hendriksen H.M.A.
        • de Leeuw F.A.
        • et al.
        Gut microbiota composition is related to AD pathology.
        Front Immunol. 2021; 12: 794519