Table 1.

Overview of the studies included for meta-analysis

Study	Included?	Figure chosen	Relevant meta-analysis	Comment
Herranz-Martin et al. [111]	Yes	Fig. S2D	Cerebellar neuronal loss	Purkinje cell counts between HRE-10 (disease control) and HRE-102
Tan et al. [93]	Yes	Table 3	Cerebellar neuronal loss	Spino- and Cerebro-cerebellum were averaged for Purkinje cells — other studies did not state a specific area of the cerebellum; therefore, both were included to avoid bias
Hao et al. [56]	Yes	Figure 5D	Cerebellar neuronal loss; DPR-related neuronal loss	Purkinje counts across an age range (averaged over time) comparing poly-PR with controls. Figure 5D — molecular layer thickness was not chosen as it is not directly neuronal counts (i.e. neuronal density could be increased in a smaller area)
Zhang et al. [69]	Yes	Fig. S3G	Cerebellar neuronal loss; DPR-related neuronal loss	Purkinje cell counts between GFP and poly-PR. Time points were averaged
May et al. [22]	Yes	Figure 3B	Dendritic arborisations	Number of dendritic crossings. All distances from the soma of dendritic crossings were averaged to give a total effect across the neuron
Park et al. [24]	Yes	Figure 1B	Dendritic arborisations	Number of dendritic branch points under different DPR transgenes (DPR effect was averaged)
Schweizer Burguete et al. [23]	Yes	Fig. S4B	Dendritic arborisations	Shows late control versus late experimental of dendritic crossings. Preferred to Fig. 3H due to similarity to May 2014
Perry et al. [44]	Yes	Figure 2J	Dendritic arborisations	Percentage retractions of synapses at the NMJ. Means were not multiplied by − 1 as, unlike other studies, a positive increase was reflective of a negative effect
O’Rourke et al. [99]	Yes	Figure 3G	Dendritic arborisations; NMJ abnormalities	Percentage of fragmented NMJs. Means were not multiplied by − 1 as, unlike other studies, a positive increase was reflective of a negative effect
LaClair et al. [80]	Yes	Figure 2E/F	DPR-related neuronal loss	Figure 2E (GA) and F (PR) were averaged to give an overall DPR effect on hippocampal neuron density as well as to avoid bias regarding which DPR was the most important
Darling et al. [77]	Yes	Figure 1A	DPR-related neuronal loss	All DPRs were averaged to compare against the control. Cell viability of iPSCs was assessed
Zhang et al. [65]	Yes	Figure 1G	DPR-related neuronal loss	Score of hippocampal neuronal loss — time points were averaged
Xu and Xu [21]	Yes	Figure 5E	NMJ abnormalities	Total bouton counts
Perry et al. [44]	Yes	Figure 1D	NMJ abnormalities	Total bouton counts. (G4C2)8 was averaged as a control, whilst (G4C2)58 and GR36/100 were averaged as experimental
Freibaum et al. [42]	Yes	Figure 1F	NMJ abnormalities	Total bouton counts — control and (G4C2)8 were averaged as this is to represent disease control
Herranz-Martin et al. [111]	Yes	Figure 3B	NMJ abnormalities	Percentage of pathological NMJs — not included for dendrites as pathological is ambiguous. HRE-10 was averaged with control. Means were not multiplied by − 1 as, unlike other studies, a positive increase was reflective of a negative effect
Frick et al. [16]	Yes	Figure 6B	Reduced C9orf72	Normalised C9orf72 levels in the cerebellum
Saberi et al. [96]	Yes	Figure 5N	Reduced C9orf72	Normalised C9orf72 levels in the frontal cortex (chosen over occipital cortex)
Belzil et al. [103]	Yes	Figure 1B	Reduced C9orf72	Normalised C9orf72 levels in the frontal cortex (chosen over CB due to frontal cortex being more widely studied)
Waite et al. [92]	Yes	Figure 3B	Reduced C9orf72	Normalised C9orf72 levels in the frontal cortex (C9-ALL was chosen over specific variants)
Yang et al. [76]	No	Figure 2B	Dendritic arborisations	Not included as only the number of neurons counted were given, not the number of animals per genotype (such as other studies) which would skew the weighting
Park et al. [24]	No	Figure 1C	Neurite length	Dendritic length — N not high enough for meta-analysis of neurite length
Zhang et al. [28]	No	Fig. S5B	Neurite length	No sample sizes were given — unable to calculate confidence intervals
Swaminathan et al. [73]	No	Figure 5B	Neurite length	Neurite length meta-analysis N was too small

Studies that are italicised had their means multiplied by − 1 as these studies measured negative effects but as a percentage (an increase in percentage is a negative outcome) and therefore were brought in line with the other studies. Abbreviations: HRE, hexanucleotide repeat expansion; GFP, green fluorescent protein; DPR, dipeptide repeat protein; NMJ, neuromuscular junction; iPSCs, induced pluripotent stem cells