Is later-life depression a risk factor for Alzheimer's disease or a prodromal symptom: a study using post-mortem human brain tissue?
Alzheimer’s disease
Amyloid
Blood–brain barrier
Dementia
Depressive disorder
Tau
Vascular depression
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
12 09 2023
12 09 2023
Historique:
received:
18
10
2022
accepted:
24
08
2023
medline:
14
9
2023
pubmed:
13
9
2023
entrez:
12
9
2023
Statut:
epublish
Résumé
Depression and dementia are both common diseases. Although new cases of depression are more common in younger adults, there is a second peak at the age of 50 years suggesting a different pathological process. Late-life depression (LLD) is associated with dementia. However, it remains unclear whether depression represents a dementia prodrome or is a true risk factor for its development. LLD is thought to have a vascular component and this may be a possible link between depression and dementia. We hypothesised that later-life depression is a prodromal manifestation of dementia and would therefore be associated with more AD, and/or ischaemic brain abnormalities that are present in earlier-life depression or in age- and sex-matched controls. We assessed post-mortem orbitofrontal cortex and dorsolateral pre-frontal cortex from 145 individuals in 4 groups: 28 18-50-year-olds with depression, 30 older individuals (ages 51-90) with depression, 28 with early AD (Braak tangle stages III-IV) and 57 matched controls (17 early-life, 42 later-life). Levels of Aβ, phospho-tau and α-synuclein were assessed by immunohistochemistry and ELISA. To quantify chronic ischaemia, VEGF, MAG and PLP1 were measured by ELISA. To assess pericyte damage, PDGFRB was measured by ELISA. For blood-brain barrier leakiness, JAM-A, claudin 5 and fibrinogen were measured by ELISA. To quantity endothelial activation, the ratio of ICAM1:collagen IV was assessed by immunohistochemistry. There was no evidence of chronic cerebral hypoperfusion or increased Aβ/tau in either depression group. There was also no indication of pericyte damage, increased blood-brain barrier leakiness or endothelial activation in the OFC or DLPFC in the depression groups. Contrary to some previous findings, we have not found evidence of impaired vascular function or increased Aβ in LLD. Our study had a relatively small sample size and limitations in the availability of clinical data. These results suggest that depression is a risk factor for dementia rather than an early manifestation of AD or a consequence of cerebral vascular insufficiency.
Sections du résumé
BACKGROUND
Depression and dementia are both common diseases. Although new cases of depression are more common in younger adults, there is a second peak at the age of 50 years suggesting a different pathological process. Late-life depression (LLD) is associated with dementia. However, it remains unclear whether depression represents a dementia prodrome or is a true risk factor for its development. LLD is thought to have a vascular component and this may be a possible link between depression and dementia. We hypothesised that later-life depression is a prodromal manifestation of dementia and would therefore be associated with more AD, and/or ischaemic brain abnormalities that are present in earlier-life depression or in age- and sex-matched controls.
METHODS
We assessed post-mortem orbitofrontal cortex and dorsolateral pre-frontal cortex from 145 individuals in 4 groups: 28 18-50-year-olds with depression, 30 older individuals (ages 51-90) with depression, 28 with early AD (Braak tangle stages III-IV) and 57 matched controls (17 early-life, 42 later-life). Levels of Aβ, phospho-tau and α-synuclein were assessed by immunohistochemistry and ELISA. To quantify chronic ischaemia, VEGF, MAG and PLP1 were measured by ELISA. To assess pericyte damage, PDGFRB was measured by ELISA. For blood-brain barrier leakiness, JAM-A, claudin 5 and fibrinogen were measured by ELISA. To quantity endothelial activation, the ratio of ICAM1:collagen IV was assessed by immunohistochemistry.
RESULTS
There was no evidence of chronic cerebral hypoperfusion or increased Aβ/tau in either depression group. There was also no indication of pericyte damage, increased blood-brain barrier leakiness or endothelial activation in the OFC or DLPFC in the depression groups.
CONCLUSIONS
Contrary to some previous findings, we have not found evidence of impaired vascular function or increased Aβ in LLD. Our study had a relatively small sample size and limitations in the availability of clinical data. These results suggest that depression is a risk factor for dementia rather than an early manifestation of AD or a consequence of cerebral vascular insufficiency.
Identifiants
pubmed: 37700368
doi: 10.1186/s13195-023-01299-2
pii: 10.1186/s13195-023-01299-2
pmc: PMC10496415
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
153Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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