{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:16:40Z","timestamp":1792516600526,"version":"4.5.0"},"reference-count":22,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordination for the Improvement of Higher Education Personnel","doi-asserted-by":"publisher","award":["88887.841787\/2023-00"],"award-info":[{"award-number":["88887.841787\/2023-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005668","name":"Foundation for Research Support of the Federal District","doi-asserted-by":"crossref","award":["623\/2022"],"award-info":[{"award-number":["623\/2022"]}],"id":[{"id":"10.13039\/501100005668","id-type":"DOI","asserted-by":"crossref"}]},{"award":["623\/2022"],"award-info":[{"award-number":["623\/2022"]}],"id":[{"id":"https:\/\/ror.org\/04djvx395","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The glymphatic system has been proposed as a brain-wide pathway that promotes the exchange between cerebrospinal and interstitial fluids and facilitates the clearance of metabolic waste products, including amyloid-\u03b2 and tau proteins. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a non-invasive magnetic resonance imaging technique proposed to indirectly assess glymphatic-related fluid dynamics. This systematic review evaluated the methodological consistency and clinical applicability of the ALPS index in neurodegenerative diseases. A structured search of PubMed (MEDLINE) and Web of Science identified human studies published up to January 2026 investigating DTI-ALPS in neurodegenerative conditions. Data regarding study populations, MRI acquisition parameters, image-processing methods, statistical approaches, and clinical associations were extracted and synthesized. Ten studies met the inclusion criteria. Across studies, lower ALPS index values were generally associated with cognitive impairment, amyloid burden, and disease severity, particularly in Alzheimer\u2019s disease. Several studies incorporated multimodal biomarkers, including amyloid positron emission tomography and cerebrospinal fluid markers, thereby improving the biological interpretation of DTI-ALPS findings. However, substantial methodological heterogeneity was identified across studies, including variability in region-of-interest placement, diffusion acquisition protocols, and image-processing pipelines. Furthermore, the interpretation of diffusivity metrics as direct measures of glymphatic flow remains controversial. Current evidence suggests that DTI-ALPS may represent a promising non-invasive imaging marker of glymphatic-related alterations; however, its biological specificity and clinical applicability remain insufficiently established. Standardized acquisition protocols, harmonized analytical pipelines, and longitudinal multicenter studies are required to clarify its role in neurodegenerative disease research.<\/jats:p>","DOI":"10.3390\/ijms27135758","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:52:11Z","timestamp":1782453131000},"page":"5758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Diffusion Tensor Imaging Along the Perivascular Space (DTI-ALPS) as a Neuroimaging Biomarker of Glymphatic Function in Neurodegenerative Diseases: A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8931-9533","authenticated-orcid":false,"given":"Raphael Lopes","family":"Oleg\u00e1rio","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Bras\u00edlia (UnB), Bras\u00edlia 70910-900, Brazil"},{"name":"Department of Clinical Medicine, Geriatric Medicine Centre, University Hospital of Bras\u00edlia, University of Bras\u00edlia (UnB), Bras\u00edlia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-7176","authenticated-orcid":false,"given":"Ot\u00e1vio Toledo","family":"N\u00f3brega","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Bras\u00edlia (UnB), Bras\u00edlia 70910-900, Brazil"},{"name":"Department of Clinical Medicine, Geriatric Medicine Centre, University Hospital of Bras\u00edlia, University of Bras\u00edlia (UnB), Bras\u00edlia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-7768","authenticated-orcid":false,"given":"Naiara Ribeiro","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Physical Education, Federal University of Juiz de Fora, Juiz de Fora 36036-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8479-7149","authenticated-orcid":false,"given":"Dany Alexis Sobarzo","family":"Soto","sequence":"additional","affiliation":[{"name":"Department of Physical Education, Federal University of Juiz de Fora, Juiz de Fora 36036-900, Brazil"},{"name":"Escuela de Kinesiologia, Universidad Santo Tom\u00e1s, Puerto Montt 5480000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9678-1977","authenticated-orcid":false,"given":"Ciro Jos\u00e9","family":"Brito","sequence":"additional","affiliation":[{"name":"Department of Physical Education, Federal University of Juiz de Fora, Juiz de Fora 36036-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6660-2766","authenticated-orcid":false,"given":"Di\u00f3genes Diego de Carvalho","family":"Bispo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Bras\u00edlia (UnB), Bras\u00edlia 70910-900, Brazil"},{"name":"Diagnostic Imaging Unit, University Hospital of Bras\u00edlia, Bras\u00edlia 70840-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1004-7641","authenticated-orcid":false,"given":"Felipe","family":"von Glehn","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Bras\u00edlia (UnB), Bras\u00edlia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7984-514X","authenticated-orcid":false,"given":"Arsenio","family":"P\u00e1ez","sequence":"additional","affiliation":[{"name":"Department of Health, Kinesiology and Applied Physiology, Concordia University, Montreal, QC H4B 1R6, Canada"},{"name":"Centre de Recherche de l\u2019Institut Universitaire de G\u00e9riatrie de Montr\u00e9al (CRIUGM), Montreal, QC H3W 1W5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7235-2721","authenticated-orcid":false,"given":"Thien Thanh","family":"Dang-Vu","sequence":"additional","affiliation":[{"name":"Department of Health, Kinesiology and Applied Physiology, Concordia University, Montreal, QC H4B 1R6, Canada"},{"name":"Centre de Recherche de l\u2019Institut Universitaire de G\u00e9riatrie de Montr\u00e9al (CRIUGM), Montreal, QC H3W 1W5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1991-5529","authenticated-orcid":false,"given":"Einstein Francisco","family":"Camargos","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Bras\u00edlia (UnB), Bras\u00edlia 70910-900, Brazil"},{"name":"Department of Clinical Medicine, Geriatric Medicine Centre, University Hospital of Bras\u00edlia, University of Bras\u00edlia (UnB), 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