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  1. Article: Human cerebral neuropathology of Type 2 diabetes mellitus.

    Nelson, Peter T / Smith, Charles D / Abner, Erin A / Schmitt, Frederick A / Scheff, Stephen W / Davis, Gregory J / Keller, Jeffrey N / Jicha, Gregory A / Davis, Daron / Wang-Xia, Wang / Hartman, Adria / Katz, Douglas G / Markesbery, William R

    Biochimica et biophysica acta

    2008  Volume 1792, Issue 5, Page(s) 454–469

    Abstract: The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review ... histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and ... or without (N = 89) the premortem diagnosis of diabetes. In diabetics, cerebrovascular pathology was ...

    Abstract The cerebral neuropathology of Type 2 diabetes (CNDM2) has not been positively defined. This review includes a description of CNDM2 research from before the 'Pubmed Era'. Recent neuroimaging studies have focused on cerebrovascular and white matter pathology. These and prior studies about cerebrovascular histopathology in diabetes are reviewed. Evidence is also described for and against the link between CNDM2 and Alzheimer's disease pathogenesis. To study this matter directly, we evaluated data from University of Kentucky Alzheimer's Disease Center (UK ADC) patients recruited while non-demented and followed longitudinally. Of patients who had come to autopsy (N = 234), 139 met inclusion criteria. These patients provided the basis for comparing the prevalence of pathological and clinical indices between well-characterized cases with (N = 50) or without (N = 89) the premortem diagnosis of diabetes. In diabetics, cerebrovascular pathology was more frequent and Alzheimer-type pathology was less frequent than in non-diabetics. Finally, a series of photomicrographs demonstrates histopathological features (including clinical-radiographical correlation) observed in brains of persons that died after a history of diabetes. These preliminary, correlative, and descriptive studies may help develop new hypotheses about CNDM2. We conclude that more work should be performed on human material in the context of CNDM2.
    MeSH term(s) Aged ; Aged, 80 and over ; Alzheimer Disease/etiology ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Animals ; Brain/blood supply ; Brain/metabolism ; Brain/pathology ; Case-Control Studies ; Cognition Disorders/etiology ; Cognition Disorders/metabolism ; Cognition Disorders/pathology ; Dementia/etiology ; Dementia/metabolism ; Dementia/pathology ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Female ; Humans ; Hypoglycemia/complications ; Hypoglycemia/metabolism ; Hypoglycemia/pathology ; Male ; Retrospective Studies
    Language English
    Publishing date 2008-08-22
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbadis.2008.08.005
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  2. Article ; Online: Review: Relationship of type 2 diabetes to human brain pathology.

    Pruzin, J J / Nelson, P T / Abner, E L / Arvanitakis, Z

    Neuropathology and applied neurobiology

    2018  Volume 44, Issue 4, Page(s) 347–362

    Abstract: Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both highly prevalent diseases worldwide ... debated. Cerebral vascular disease (CVD) is likely to be playing a role. But increased AD neuropathologic ... to further disentangle the relationship of T2D to dementia in the ageing human brain. ...

    Abstract Type 2 diabetes (T2D) and Alzheimer's disease (AD) are both highly prevalent diseases worldwide, and each is associated with high-morbidity and high-mortality. Numerous clinical studies have consistently shown that T2D confers a two-fold increased risk for a dementia, including dementia attributable to AD. Yet, the mechanisms underlying this relationship, especially nonvascular mechanisms, remain debated. Cerebral vascular disease (CVD) is likely to be playing a role. But increased AD neuropathologic changes (ADNC), specifically neuritic amyloid plaques (AP) and neurofibrillary tangles (NFT), are also posited mechanisms. The clinicopathological studies to date demonstrate T2D to be consistently associated with infarcts, particularly subcortical lacunar infarcts, but not ADNC, suggesting the association of T2D with dementia may largely be mediated through CVD. Furthermore, growing interest exists in insulin resistance (IR), particularly IR within the brain itself, which may be an associated but distinct phenomenon from T2D, and possibly itself associated with ADNC. Other mechanisms largely related to protein processing and efflux in the central nervous system with altered function in T2D may also be involved. Such mechanisms include islet amyloid polypeptide (or amylin) deposition, co-localized with beta-amyloid and found in more abundance in the AD temporal cortex, blood-brain barrier breakdown and dysfunction, potentially related to pericyte degeneration, and disturbance of brain lymphatics, both in the glial lymphatic system and the newly discovered discrete central nervous system lymph vessels. Medical research is ongoing to further disentangle the relationship of T2D to dementia in the ageing human brain.
    MeSH term(s) Alzheimer Disease/etiology ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Brain/metabolism ; Brain/pathology ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Humans ; Neurofibrillary Tangles/metabolism ; Neurofibrillary Tangles/pathology ; Plaque, Amyloid/metabolism ; Plaque, Amyloid/pathology ; tau Proteins/metabolism
    Chemical Substances Amyloid beta-Peptides ; tau Proteins
    Language English
    Publishing date 2018-03-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 80371-6
    ISSN 1365-2990 ; 0305-1846
    ISSN (online) 1365-2990
    ISSN 0305-1846
    DOI 10.1111/nan.12476
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    Zs.A 1241: Show issues Location:
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