Department of Pathology, Uppsala University Hospital, Sweden.
Department of Immunology, Genetics and Pathology, Uppsala University, Sweden.
J Alzheimers Dis. 2020;78(1):453-465. doi: 10.3233/JAD-200925.
Systemic diseases, diabetes mellitus (DM), and cardiovascular disease (CaVD) have been suggested being risk factors for cognitive impairment (CI) and/or influence Alzheimer's disease neuropathologic change (ADNC).
The purpose was to assess the type and the extent of neuropathological alterations in the brain and to assess whether brain pathology was associated with CaVD or DM related alterations in peripheral organs, i.e., vessels, heart, and kidney.
119 subjects, 15% with DM and 24% with CI, age range 80 to 89 years, were chosen and neuropathological alterations were assessed applying immunohistochemistry.
Hyperphosphorylated τ (HPτ) was seen in 99%, amyloid-β (Aβ) in 71%, transactive DNA binding protein 43 (TDP43) in 62%, and α-synuclein (αS) in 21% of the subjects. Primary age related tauopathy was diagnosed in 29% (more common in females), limbic predominant age-related TDP encephalopathy in 4% (14% of subjects with CI), and dementia with Lewy bodies in 3% (14% of subjects with CI) of the subjects. High/intermediate level of ADNC was seen in 47% and the extent of HPτ increased with age. The extent of ADNC was not associated with the extent of pathology observed in peripheral organs, i.e., DM or CaVD. Contrary, brain alterations such as pTDP43 and cerebrovascular lesions (CeVL) were influenced by DM, and CeVL correlated significantly with the extent of vessel pathology.
In most (66%) subjects with CI, the cause of impairment was "mixed pathology", i.e., ADNC combined with TDP43, αS, or vascular brain lesions. Furthermore, our results suggest that systemic diseases, DM and CaVD, are risk factors for CI but not related to ADNC.
全身性疾病、糖尿病（DM）和心血管疾病（CaVD）已被认为是认知障碍（CI）的危险因素，或影响阿尔茨海默病神经病理改变（ADNC）。
评估大脑的病理类型和程度，并评估脑病理是否与 CaVD 或 DM 相关的外周器官改变（即血管、心脏和肾脏）相关。
选择了 119 名年龄在 80 至 89 岁之间的受试者，其中 15%患有 DM，24%患有 CI，应用免疫组织化学方法评估神经病理改变。
99%的受试者出现磷酸化 tau（HPτ），71%出现淀粉样蛋白-β（Aβ），62%出现反式激活 DNA 结合蛋白 43（TDP43），21%出现 α-突触核蛋白（αS）。29%的受试者被诊断为原发性年龄相关性 tau 病（更常见于女性），4%的受试者被诊断为边缘优势型年龄相关性 TDP 脑病（14%的 CI 受试者），3%的受试者被诊断为路易体痴呆（14%的 CI 受试者）。ADNC 高级/中级水平见于 47%，HPτ的程度随年龄增加而增加。ADNC 的程度与外周器官（即 DM 或 CaVD）观察到的病理程度无关。相反，脑改变如 pTDP43 和脑血管病变（CeVL）受 DM 影响，CeVL 与血管病理程度显著相关。
在大多数（66%）患有 CI 的受试者中，损伤的原因是“混合性病理”，即 ADNC 与 TDP43、αS 或血管性脑病变结合。此外，我们的结果表明，全身性疾病、DM 和 CaVD 是 CI 的危险因素，但与 ADNC 无关。
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